UNIT VI

NEUROBIOLOGY OF BEHAVIOUR: Neurological Aspects Of Drives, Motivation,

Hunger, Thirst, Sex, Emotions, Learning And Memory.

DRIVES &

MOTIVATION

Motivation, defined as the energizing of behavior in pursuit of a goal, is a

fundamental element of our interaction with the world and with each other. All
animals share motivation to obtain their basic needs, including food, water, sex and
social interaction. Meeting these needs is a requirement for survival, but in all cases
the goals must be met in appropriate quantities and at appropriate times.
According to instinct approaches to motivation, people and animals are born
preprogrammed with sets of behaviors essential to their survival. Therefore
motivational drive must be modulated as a function of both internal states as well
as external environmental conditions. The regulation of motivated behaviors is
achieved by the coordinated action of molecules (peptides, hormones,
neurotransmitters etc), acting within specific circuits that integrate multiple signals
in order for complex decisions to be made.

One of the earliest psychological theories of motivation, Hull’s drive theory, posited
that behaviors occur to reduce biological needs, thereby optimizing the organism’s
potential for survival. However in Hull’s theory, motivational drive functioned solely
to energize responding, drive was not responsible for initiating, or maintaining the
direction of action. Later, motivation was conceptualized to consist of both a goal-
directed, directional component and an arousal, activational component.

There are two aspects of motivation have both common and distinctive neural
underpinnings. For example, circadian factors may energize the general motive of
seeking food or mate, but the specific actions that occur in pursuit of these goals
are regulated by different substrates. Similarly, local cues that signal food
availability may energize many food seeking actions, signals for specific foods
differentially energize actions associated with obtaining the specific outcome. Again,
the neural substrates of the general and specific effects are somewhat distinctive.
At each level, whole classes of specific actions are made more or less likely by these
factors. We suggest that there is generally a hierarchical structure to motivation in
the sense that general arousal factors such as sleep–wake cycles will affect many
different motives, that activation of specific motives (e.g., hunger, thirst, social
motives) can activate many specific actions that could lead to many specific
outcomes within a general class of goals, and that more temporally and situationally
specific factors determine the specific actions that occur in pursuit of that goal.

APPROACHES TO MOTIVATION

 Drive-Reduction Approaches: Satisfying Our Needs

After rejecting instinct theory, psychologists first proposed simple drive-reduction
theories of motivation to take its place (Hull, 1943). Drive-reduction approaches
to motivation suggest that a lack of some basic biological requirement such as water
produces a drive to obtain that requirement (in this case, the thirst drive). A drive
is motivational tension, or arousal, that energizes behavior to fulfil a need. Many
basic drives, such as hunger, thirst, sleep, and sex, are related to biological needs of
the body or of the species as a whole. These are called primary drives. Primary
drives contrast with secondary drives in which behavior fulfils no obvious biological
need. In secondary drives, prior experience and learning bring about needs. For
instance, some people have strong needs to achieve academically and professionally.
We can say that their achievement need is reflected in a secondary drive that
motivates their behaviour.

Homeostasis
Homeostasis, the body’s tendency to maintain a steady internal state,
underlies primary drives. Using feedback loops, homeostasis brings deviations
in body functioning back to an optimal state, similar to the way a thermostat
and a furnace work in a home heating system to maintain a steady
temperature (see Figure 1). Receptor cells throughout the body constantly
monitor factors such as temperature and nutrient levels. When deviations
from the ideal state occur, the body adjusts in an effort to return to an
optimal state. Many fundamental needs, including the needs for food, water,
stable body temperature, and sleep, operate via homeostasis.

 Arousal Approaches: Beyond Drive Reduction

Arousal approaches seek to explain behavior in which the goal is to maintain or
increase excitement. According to arousal approaches to motivation, each person
tries to maintain a certain level of stimulation and activity. As with the drive
reduction model, this model suggests that if our stimulation and activity levels
become too high, we try to reduce them. But, in contrast to the drive-reduction
model, the arousal model also suggests that if levels of stimulation and activity are
too low, we will try to increase them by seeking stimulation. People vary widely in
the optimal level of arousal they seek out, with some people looking for especially
high levels of arousal. For example, people who participate in daredevil sports, high-
stakes gamblers, and criminals who pull off high-risk robberies may be exhibiting a
particularly high need for arousal.

 Incentive Approaches: Motivation’s Pull

Theories suggesting that motivation stems from the desire to obtain valued external
goals, or incentives. In this view, the desirable properties of external stimuli—
whether grades, money, affection, food, or sex—account for a person’s motivation.

 Cognitive Approaches: The Thoughts Behind Motivation

Cognitive approaches to motivation suggest that motivation is a product of people’s
thoughts, expectations, and goals—their cognitions. For instance, the degree to
which people are motivated to study for a test is based on their expectation of how
well studying will pay off in terms of a good grade. Cognitive theories of motivation
draw a key distinction between intrinsic and extrinsic motivation. Intrinsic
motivation causes us to participate in an activity for our own enjoyment rather
than for any concrete, tangible reward that it will bring us. In contrast, extrinsic
motivation causes us to do something for money, a grade, or some other concrete,
tangible reward. For example, when a physician works long hours because she loves
medicine, intrinsic motivation is prompting her; if she works hard to make a lot of
money, extrinsic motivation underlies her efforts.

 Maslow’s Hierarchy: Ordering Motivational Needs

Maslow’s model places motivational needs in a hierarchy and suggests that before
more sophisticated, higher-order needs can be met, certain primary needs must
be satisfied (Maslow, 1970, 1987). A pyramid can represent the model with the
more basic needs at the bottom and the higher-level needs at the top. To activate
a specific higher-order need, thereby guiding behavior, a person must first fulfil the
more basic needs in the hierarchy.
The basic needs are primary drives: needs for water, food, sleep, sex, and the like.
To move up the hierarchy, a person must first meet these basic physiological needs.
Safety needs come next in the hierarchy; Maslow suggests that people need a safe,
secure environment in order to function effectively. Physiological and safety needs
compose the lower-order needs. Only after meeting the basic lower-order needs
can a person consider fulfilling higher-order needs, such as the needs for love and
a sense of belonging, esteem, and self-actualization. Love and belongingness needs
include the needs to obtain and give affection and to be a contributing member of
some group or society. After fulfilling these needs, a person strives for esteem. In
Maslow’s thinking, esteem relates to the need to develop a sense of self-worth by
recognizing that others know and value one’s competence.
Once these four sets of needs are fulfilled—no easy task—a person is able to strive
for the highest-level need, self-actualization. Self-actualization is a state of self-
fulfilment in which people realize their highest potentials in their own unique way.
Although Maslow first suggested that self-actualization occurred in only a few
famous individuals, he later expanded the concept to encompass everyday people.
For example, a parent with excellent nurturing skills who raises a family, a teacher
who year after year creates an environment that maximizes students’ opportunities
for success, and an artist who realizes his creative potential all may be self-
actualized. The important thing is that people feel at ease with themselves and
satisfied that they are using their talents to the fullest. In a sense, achieving self-
actualization reduces the striving and yearning for greater fulfilment that mark
most people’s lives and instead provides a sense of satisfaction with the current
state of affairs.
Edward Deci and Richard Ryan (2008) have considered human needs in
terms of psychological well-being. They suggest in their self-determination theory
that people have the three basic needs of competence, autonomy, and relatedness.
Competence is the need to produce desired outcomes, while autonomy is the
perception that we have control over our own lives. Finally, relatedness is the need
to be involved in close, warm relationships with others. In the view of self-
determination theory, these three psychological needs are innate and universal
across cultures, and they are essential as basic biological needs
HOW MOTIVATION MIGHT WORK IN THE BRAIN

Many different factors influence motivation, including the organism’s internal

physiological states, the current environmental conditions, as well as the organism’s
past history and experiences.

A simplified diagram of the influencing factors and processes that are involved in
motivation. This framework of motivation places cost–benefit analysis central to
the concept of motivation. Three major categories of factors are known to influence
motivation: the individual’s physiological state, the environment, and the
individual’s past history. Information about all 3 categories of factors will be subject
to a number of processes (represented inside the blue oval), including evaluation
and encoding. In almost all circumstances, the motive, environment, and
physiological state will not be novel; therefore, information will also undergo
learning and retrieval processes. All of the combined processes result in weighting
of all the costs and benefits related to the motive, and the output of the cost–
benefit calculation will impact upon the direction and vigor of action that the
individual takes toward the motive goal.
Information about all 3 categories of factors will be subject to a number of processes
(represented inside the oval), including evaluation and encoding. In almost all
circumstances, the motive, environment, and physiological state will not be novel;
therefore, information will also undergo learning and retrieval processes.
The costs associated with behavioral action may include physical effort, mental
effort, time, loss of potential opportunities, discomfort, and danger (the risk of
pain and potential death). The benefits associated with behavioral action might
include fulfilling physiological and psychological needs, obtaining reinforcement
secondary to those needs, escaping from harm, or avoidance of some of the costs
listed above. As mentioned above, information entering the cost–benefit
computation for any specific motive will be processed in several ways. The value of
every cost and every benefit must be calculated and encoded.
It is important to consider that value must be encoded when a goal is obtained and
then stored for future retrieval when obtaining that goal again becomes relevant.
When that happens in the current moment, the assessment of value must be
conditioned both on this past experience as well as the current state and
environmental conditions. Goals are likely to be obtained with some temporal
distance from the initiation, or even conclusion of behavioral output. Single neuron
activity in several brain regions including orbitofrontal cortex, anterior cingulate,
and basolateral amygdala has been shown to correlate with reward prediction and
this work is reviewed by Bissonette and Roesch in this volume. The encoded values
of costs and benefits do not belong in absolute scales because the values of all costs
and benefits are rendered relative to the animal’s current physiological state as well
as the current conditions of the surrounding environment.

ROLE OF REWARD

 One of the most powerful variables influencing motivation is reward,

irrespective of reward type (physical or social reward). The main function of
reward is to induce positive emotions, make the organism approach, increase
the frequency of the target behavior, and hence prevent extinction.
 The reward processing consists of a sequence of sub processes such as
anticipating the reward, associating reward with behavior, planning to obtain
the reward, encoding the value of reward, and updating the relative value of
reward.

NEUROBIOLOGY OF MOTIVATION
 DOPAMINERGIC REWARD SYSTEM
Since dopamine (DA) was described as a neurotransmitter in the central nervous
system half a century ago (Carlsson, 1959), its involvement in movement control
has long been emphasized due to the association between the amount of striatal
DA depletion and motor deficits observed in Parkinson's disease (PD) (Bernheimer,
1965)

It is known that DA is involved in the neurobiology and symptoms of a myriad of

neurological and psychiatric diseases, including schizophrenia and attention deficit
hyperactivity disorder, and it is being considered an essential element in the brain
reward system and in the action of many drugs with abuse potential

Although dopaminergic neurons account for less than 1% of the total neuronal
population of the brain (Arias-Carrion, 2007), they have a profound effect on
brain function. For instance, there are modifications of synaptic plasticity as a
consequence of learning and memory due to the activity of the metabotropic DA
receptors (Arias-Carrion, 2007).

Learning is a change in responsiveness to a particular stimulus whereas memory is

the cellular modification that mediates that change. In this regard, recent evidence
indicates that DA is involved in reward-related incentive learning (Pessiglione,
2007). However, the mechanism involving DA modulating behavioural choice
towards available rewards remains unknown.
Rewards are defined as those objects, which we will work to acquire through
allocation of time, energy, or effort; that is, any object or goal that we seek.
Rewards are crucial for individual and support elementary processes such as
drinking, eating and reproduction.

The behavioural definition of reward attributes also certain of non-alimentary and

nonsexual functions, such as gambling. Rewards engage agents in such diverse
behaviours as foraging and trading on stock markets (Schultz, 2010).

Due to this requirement, it has been proposed that there exists a single neural
system which processes rewards in its different modalities and thereby functions as
a common scale through which diverse rewards may be contrasted (Shizgal, 1997).

Several lines of evidence support the conclusion that the brain's mesencephalic DA
system responds to rewards. It has been demonstrated that DA is involved in the
hedonic component of reward (Phillips, 2008) Several lines of evidence show that
the receipt of rewards evokes an increase in DA activity.

It has been suggested that activity changes in DA neurons encode an error in the
prediction of the time and amount of immediate and future rewards (the
prediction error hypothesis), therefore, the DA activity is hypothesized to indicate
that the immediate or future prospect for reward is better than expected.

 THE MESO-CORTICO-LIMBIC DOPAMINE SYSTEM

In the adult brain, dopaminergic neurons are a heterogeneous group of cells
localized in the mesencephalon, diencephalon and the olfactory [Link],
nearly all DA cells reside in the ventral part of the mesencephalon. Meso-
diencephalic dopaminergic neurons form substantia nigra pars compacta (SNc), the
ventral tegmental area (VTA) and the retrorubral field (RRF).

Additionally, the nigrostriatal system, which originates in the SNc and extends its
fibers into the caudate-putamen nucleus, plays an essential role in the control of
voluntary movement.

The DA system includes the mesolimbic and mesocortical pathway, which arise
from VTA and they have been suggested to modulate emotion-related behavior.
The mesolimbic dopaminergic system includes VTA that project mainly to the
nucleus accumbens (NAc) as well as the olfactory tubercle innervating the septum,
amygdala and hippocampus.
On the other hand, the mesocortical dopaminergic system which includes the VTA,
extends its fibers in the prefrontal, cingulate and perirhinal cortex. Because of the
overlap between these two systems they are often collectively referred to as the
mesocorticolimbic system.

OVERVIEW OF BRAIN AREAS:

 The primary brain regions associated with reward is the dopamine pathway
widely known as reward pathway.
 Dopamine is a neurotransmitter that is produced in the ventral tegmental
area (VTA), passes through the globus pallidus and released into the nucleus
accumbens (NAcc) located in the striatum
 o These dopaminergic neurons are projected in VTA as the mesolimbic
system to the nucleus accumbens (NAcc) and to the frontal cortex as
the mesocortical system.
 Mesolimbic dopamine system is where ventral tegmentum area (VTA) neurons
are connected to the Nucleus accumbens (NAcc), the septum, the amygdala,
and the hippocampus. This system is responsible for reward anticipation and
learning
o The mesolimbic system is thought to signal the hedonic (pleasurable or
positively reinforcing) qualities of a stimulus such as food or drink, on
the basis of internal states and external reinforcers, activating the
appropriate goalseeking behavior
o The nucleus accumbens forms part of the anterior cingulate (affective)
basal ganglia circuit which is thought to translate motivation into the
motor activity appropriate to the goal-directed behavior, with the
motivation signal provided by the mesolimbic system. So, for example,
when hungry we are more likely to find, prepare and consume food
than if we have recently eaten.
o However, the mesolimbic system is more sophisticated than this. Firing
of mesolimbic neurons in response to a natural reward (e.g. fruit juice)
or a conditional stimulus – light or tone – with which this has been
paired, depends on the predictability of the reward.
 Mesocortical dopamine system is the linkage between the medial prefrontal
cortex (MPFC), the ACC, and the perirhinal cortex. This system involves in
encoding the relative value of the reward and goal-directed behavior.
 The Orbito-frontal cortex (OFC), the amygdala, and the NAcc are the brain
regions that are consistently reported to be involved in reward processing
(e.g., Haber and Knutson, 2010).
 The Dorsolateral prefrontal cortex (DLPFC), the Medial Prefrontal cortex
(MPFC), and the Anterior cingulate cortex (ACC) are also reported to be
relevant to reward processing, but the primary functions of these areas are
more to do with the executive function in achieving the goal.
 The OFC-amygdala-NAcc system responds to both primary rewards such as
food or sexual excitement and to secondary rewards like money and social
rewards including verbal praise or cooperation
 In particular, the NAcc known as the pleasure center is activated when a
variety of rewards are anticipated or received.
 o For instance, the NAcc is activated when people were presented with
favorite stimulus, engaged in favored activity, smoking, hearing jokes,
and even when feeling love
 In contrast, several studies show that amygdala, which is known to respond
to conditions associated with fear and negative stimulus, is intensity-sensitive
not valence-sensitive
 In case of primary reward, which is essential for survival that all the species
are automatically programmed to approach it, the ventral striatum including
the NAcc forms an association of behavior-outcome.
 The OFC is the critical brain region for value judgment. In particular, the
medial OFC is reward-sensitive, whereas the lateral OFC is punishment-
sensitive.
 OFC does not respond to the absolute value of the reward but it calculates
the relative value of the reward and respond only to the ones with higher
preference

Overview of reward structures in the human brain

Dopaminergic neurons are located in the midbrain structures substantia nigra (SNc)
and the ventral tegmental area (VTA). Their axons project to the striatum (caudate
nucleus, putamen and ventral striatum including nucleus accumbens), the dorsal
and ventral prefrontal cortex.

Additional brain structures influenced by reward include the supplementary motor

area in the frontal lobe, the rhinal cortex in the temporal lobe, the pallidum and
subthalamic nucleus in the basal ganglia, and a few others.

Thus, it has been proved that ascending dopaminergic neurons are responsible for
activating motivated behaviour. As discussed above, the dopaminergic neurons in
the ventral tegmental area (VTA) project to the nucleus accumbens (ventral
striatum) as the mesolimbic system and to the frontal cortex as the mesocortical
system.

The mesolimbic system is thought to signal the hedonic (pleasurable or positively

reinforcing) qualities of a stimulus such as food or drink, on the basis of internal
states and external reinforcers, activating the appropriate goalseeking behavior.
Evidence for this includes:
1. Firing of neurons in the mesolimbic system is increased by the presence of natural
reinforcers such as food.

2. Injection of amphetamine (which elevates synaptic concentrations of dopamine)

into the nucleus accumbens increases motivated behaviors.

3. Surgical or chemical (6-hydroxy dopamine) lesions of the mesolimbic pathway,

reduces appetitive behavior.

4. Intracranial self-stimulation (ICSS), in which electrodes are chronically

implanted into rat brains and the animals learn to press a lever to deliver a small
stimulating current through the electrode. When the electrode is in the medial
forebrain bundle (MFB), which contains the mesolimbic axons, the rats lever-press
up to 100 times per minute. Given the choice between food or sex and ICSS, suitably
deprived rats choose ICSS, which implies that it is a very powerful reinforcer.

5. ICSS, natural rewards and addictive drugs all increase the release of dopamine
from mesolimbic terminals in the nucleus accumbens, and the reinforcing properties
of all three are blocked by dopamine D1 receptor antagonists.

The nucleus accumbens forms part of the anterior cingulate (affective) basal ganglia
circuit which is thought to translate motivation into the motor activity appropriate
to the goal-directed behavior, with the motivation signal provided by the
mesolimbic system. So, for example, when hungry we are more likely to find,
prepare and consume food than if we have recently eaten.

However, the mesolimbic system is more sophisticated than this. Firing of

mesolimbic neurons in response to a natural reward (e.g. fruit juice) or a conditional
stimulus – light or tone – with which this has been paired, depends on the
predictability of the reward.

Unexpected or novel rewards elicit a strong response which declines with repeated
presentation. Perhaps this explains why we eat more of a meal that consists of six
courses of gourmet foods than a single bowl of rice. Predicted rewards have little
effect, but omission of a predicted reward reduces mesolimbic activity.

The immediate response to omission of an expected reward is to persevere with the

operation that usually provides it. So, low activity of mesolimbic neurons when a
predicted reward is missed could be a signal not to switch from the current focus
of attention.
Most goal-directed motivation, even the seeking of food or water, is learned (Hall,
2002). It is largely through selective reinforcement of initially random movements,
that the behavior of the neonate comes to be both directed at and motivated by
appropriate stimuli in the environment.

For the most part, one's motivation is to return to the rewards experienced in the
past, and to the cues that mark the way to such rewards. It is primarily through
its role in the selective reinforcement of associations between rewards and otherwise
neutral stimuli that DA is important for such motivation.

Once stimulus-reward associations have been formed, they can remain potent for
some time even after the reward has been devalued by the absence of appropriate
drive states such as hunger or thirst (Changizi, 2002), or because the DA system
is blocked (Dickinson, 2000).

Once a habit has been established, it remains largely autonomous until the
conditioned significance of incentive motivational stimuli has been extinguished or
devalued throught experience.
HUNGER

Different species use different eating strategies. Digestion is the complex process of
turning the food you eat into nutrients, which the body uses for energy, growth and
cell repair needed to survive. The digestion process also involves creating waste to be
eliminated.

The digestive system includes the mouth, pharynx (throat), esophagus, stomach,
small intestine, large intestine, rectum, and anus. It also includes the salivary
glands, liver, gallbladder, and pancreas, which make digestive juices and enzymes
that help the body digest food and liquids.

Digestion begins in the mouth, where enzymes in the saliva break down
carbohydrates. Swallowed food travels down the esophagus to the stomach, where
it mixes with hydrochloric acid and enzymes that digest proteins. The stomach
stores food for a time, and then a round sphincter muscle opens at the end of the
stomach to release food to the small intestine. The small intestine has enzymes that
digest proteins, fats, and carbohydrates. It is also the site for absorbing digested
materials into the bloodstream. The blood carries those chemicals to body cells that
either use them or store them for later use. The large intestine absorbs water and
minerals and lubricates the remaining materials to pass as faeces.

Enzymes and Consumption of Dairy Products

Most mammals at about the age of weaning lose the intestinal enzyme lactase,
which is necessary for metabolizing lactose, the sugar in milk. From then on, milk
consumption causes stomach cramps and gas– lactose intolerance. Humans are a
partial exception to this rule. Many adults have enough lactase levels to consume
milk and other dairy products throughout life. Worldwide, however, most adults
cannot comfortably tolerate large amounts of milk products. Most human beings,
after all, are Asians, and nearly all the people in China and surrounding countries
lack the gene that enables adults to metabolize lactose. Humans are a partial
exception to this rule. Many adults have enough lactase levels to consume milk and
other dairy products throughout life. Worldwide, however, most adults cannot
comfortably tolerate large amounts of milk products. Most human beings, after all,
are Asians, and nearly all the people in China and surrounding countries lack the
gene that enables adults to metabolize lactose.
SHORT TERM AND LONG TERM REGUALTION OF FEEDING

Eating is far too important to be entrusted to just one mechanism. Your brain gets
messages from your mouth, stomach, intestines, fat cells, and elsewhere to regulate
your eating.

 Oral Factors - taste and other mouth sensations contribute to satiety, but
they are not enough by themselves such as the act of chewing.

 The Stomach and Intestines

Usually, the main signal to end a meal is distension of the stomach. The stomach
conveys satiety messages to the brain via the vagus nerve and the splanchnic nerves.
The vagus nerve (cranial nerve X) conveys information about the stretching of the
stomach walls, providing a major basis for satiety. The splanchnic nerves convey
information about the nutrient contents of the stomach. However, people who have
had their stomach surgically removed (because of stomach cancer or other disease)
still report satiety, so stomach distension can’t be necessary for satiety. Later
researchers found that meals end after distension of either the stomach or the
duodenum. The duodenum is the part of the small intestine adjoining the stomach.
It is the first digestive site that absorbs a significant amount of nutrients. Food in
the duodenum releases the hormone cholecystokinin (CCK), which limits meal size
in two ways. First, CCK closes the sphincter muscle between the stomach and the
duodenum, causing the stomach to hold its contents and fill more quickly than
usual. Second, CCK stimulates the vagus nerve, which sends a message to the
hypothalamus, causing cells there to release a neurotransmitter that is a shorter
version of the CCK molecule itself.

 Glucose, Insulin, and Glucagon

Much digested food enters the bloodstream as glucose, an important source of
energy throughout the body and nearly the only fuel used by the brain. When the
blood’s glucose level is high, liver cells convert some of the excess into glycogen, and
fat cells convert some of it into fat. When the blood’s glucose level starts to fall, the
liver converts some of its glycogen back into glucose. So blood glucose levels stay
fairly steady for most people most of the time.
Two pancreatic hormones, insulin
and glucagons, regulate the flow of
glucose. Insulin enables glucose to
enter the cells, except for brain
cells, where glucose does not need
insulin to enter. When insulin levels
are high, cells receive glucose
easily. When someone is getting
ready for a meal, insulin levels rise,
letting some of the blood glucose
enter the cells in preparation for
the rush of additional glucose
about to enter the blood. Insulin
increases even more during and
after a meal. As you might guess,
high levels of insulin tend to
decrease appetite. When much
glucose is already entering the cells, you don’t need to eat more.

As time passes after a meal,

the blood glucose level falls.
Therefore, insulin levels
drop, glucose enters the cells
more slowly, and hunger
increases. Glucagon
stimulates the liver to
convert some of its stored
glycogen to glucose to
replenish low supplies in the
blood.
If the insulin level stays
constantly high, the body
continues rapidly moving
blood glucose into the cells,
including the liver cells and
fat cells, long after a meal.
Consequently, blood glucose drops and
hunger increases in spite of the high
insulin level.

If the insulin level remains constantly

low, as in people with diabetes, blood
glucose levels may be three or more
times the normal level, but little of it
enters the cells.
People and animals with diabetes eat
more food than normal because their
cells are starving, but they excrete
most of their glucose, and they lose
weight.

 Leptin

It is a long term regulation system. It does so by monitoring fat supplies. The body’s
fat cells produce leptin. The more fat cells, the more leptin. Mice with the obese
gene fail to produce leptin. Leptin signals the brain about the body’s fat reserves,
providing a long-term indicator of whether meals have been too large or too small.
Each meal also increases the release of leptin, so the amount of circulating leptin
indicates something about short-term nutrition as well. When leptin levels are high,
animals act as if they have plenty of nutrition. They eat less, become more active,
and increase the activity of their immune systems.

BRAIN MECHANISM OF HUNGER

Hunger depends on the contents of your stomach and intestines, the availability of
glucose to the cells, and your body’s fat supplies, as well as your health and body
temperature. The key areas for making this decision include several nuclei of the
hypothalamus.
The Arcuate Nucleus and Paraventricular Hypothalamus
Many kinds of information impinge onto two kinds of cells in the arcuate nucleus
of the hypothalamus, which is regarded as the “master area” for control of appetite.
Axons extend from the arcuate nucleus to other areas of the hypothalamus.

The arcuate nucleus of the hypothalamus has one set of neurons sensitive to hunger
signals and a second set sensitive to satiety signals. The hunger-sensitive cells receive
input from the taste pathway; you have surely noticed that good-tasting food
stimulates your hunger. Another input to the hunger-sensitive cells comes from
axons releasing the neurotransmitter ghrelin. The stomach releases ghrelin during
a period of food deprivation, where it triggers stomach contractions. Ghrelin also
acts on the hypothalamus to decrease appetite and acts on the hippocampus to
enhance learning. Whereas the digestive system secretes several hormones that
signal satiety, ghrelin is the only known hunger hormone.
Much of the output from the arcuate nucleus goes to the paraventricular nucleus
of the hypothalamus. The paraventricular nucleus (PVN) inhibits the lateral
hypothalamus, an area important for eating. So the paraventricular nucleus is
important for satiety.

The Lateral Hypothalamus

Output from the paraventricular nucleus acts on the lateral hypothalamus, which
controls insulin secretion, alters taste responsiveness, and facilitates feeding in other
ways. An animal with damage in this area refuses food and water, averting its head
as if the food were distasteful. The animal may starve to death unless it is force-
fed, but if kept alive, it gradually recovers much of its ability to eat.
Role:
 Alter the taste sensation and the salivation response to the tastes,
 Facilitating ingestion and swallowing and causing cortical cells to increase
their response to the taste, smell, or sight of food,
 Increases the pituitary gland’s secretion of hormones that increase insulin
secretion,
 Controlling autonomic responses such as digestive secretions.

Medial Areas of the Hypothalamus

A large lesion centered on the ventromedial hypothalamus (VMH) leads to
overeating and weight gain. In contrast, those with damage in the ventromedial
area eat normal-sized meals, but they eat more frequently.

EATING DISORDERS

 Obesity- can be traced to the effects of a single gene. The most common of
these is a mutated gene for the receptor to melanocortin, one of the
neuropeptides responsible for hunger. People with a mutation in that gene
overeat and become obese from childhood onward.
Syndromal obesity is obesity that results from a medical condition, or
syndrome. For example, damage to parts of the temporal and frontal cortex
often leads to overeating, among other problems.
Prader-Willi syndrome is a genetic condition marked by mental retardation,
short stature, and obesity. People with this syndrome have blood levels of
ghrelin.
 Weight loss- Dieting, by itself, is not reliably effective. If diet and exercise fail
to help someone lose weight, another option is weight-loss drugs. For years,
the most effective combination was “fen-phen”: Fenfluramine increases the
release of serotonin and blocks its reuptake. Phentermine blocks reuptake of
norepinephrine and dopamine and therefore prolongs their activity. The fen-
phen combination produces brain effects similar to those of a completed meal.
Surgery is worth considering only in severe cases of obesity.
 Anorexia nervosa - People with anorexia nervosa are unwilling to eat as much
as they need. They become extremely thin and in some cases die. The problem
is a fear of becoming fat or of losing self-control. Most people with anorexia
 are hardworking perfectionists who are amazingly active, unlike other people
on the verge of starvation.
 Bulimia nervosa- Bulimia nervosa is a condition in which people alternate
between extreme dieting and binges of overeating. About 95% of people with
bulimia also have at least one other psychiatric disorder, such as depression
or anxiety. Bulimia requires ready availability of large quantities of very tasty
foods, especially fats and carbohydrates. Some (not all) people with bulimia
force themselves to vomit after huge meals. Repeated overeating and vomiting
can endanger one’s health.
THIRST

Water constitutes about 70% of the mammalian body. Because the concentration
of chemicals in water determines the rate of all chemical reactions in the body, the
water must be regulated within narrow limits. The body also needs enough fluid in
the circulatory system to maintain normal blood pressure. People sometimes survive
for weeks without food, but not without water.
A regulatory mechanism contains four essential features: the system variable (the
characteristic to be regulated), a set point (the optimal value of the system
variable), a detector that monitors the value of the system variable, and a
correctional mechanism that restores the system variable to the set point. Negative
feedback is an essential characteristic of all regulatory

MECHANISM OF WATER REGUALTION

Different species have different strategies for maintaining the water they need. We
humans vary our strategy depending on circumstances. If you cannot find enough
to drink or if the water tastes bad, you conserve water by excreting more
concentrated urine, decreasing your sweat, and other autonomic responses.
Your posterior pituitary releases a hormone called vasopressin, which raises blood
pressure by constricting the blood vessels. (The term vasopressin comes from
vascular pressure.) The increased pressure helps compensate for the decreased
volume. Vasopressin is also known as antidiuretic hormone (ADH) because it enables
the kidneys to reabsorb water from urine and therefore make the urine more
concentrated. (Diuresis means “urination.”)
In most cases, we drink more than we need and excrete the excess. (However, if
you drink extensively without eating, as many alcoholics do, you may excrete
enough body salts to harm yourself.) Most of our drinking is with meals or in social
situations, and most people seldom experience intense thirst.
We distinguish two types of thirst.
1. Eating salty foods causes osmotic thirst, and
2. Losing fluid, such as by bleeding or sweating, induces hypovolemic thirst.

OSMOTIC THIRST
The combined concentration of all solutes (molecules in solution) in mammalian
body fluids remains at a nearly constant level of 0.15 M (molar). Any deviation
activates mechanisms that restore the concentration of solutes to the set point.
Osmometric thirst occurs when the solute concentration of the interstitial fluid
increases. The term osmometric refers to the fact that the detectors are actually
responding to (metering) changes in the concentration of the interstitial fluid that
surrounds them. The solutes inside and outside a cell produce an osmotic pressure,
the tendency of water to flow across a semipermeable membrane from the area of
low solute concentration to the area of higher concentration. A semipermeable
membrane is one through which water can pass but solutes cannot. The membrane
surrounding a cell is almost a semipermeable membrane because water flows across
it freely and various solutes flow either slowly or not at all between the intracellular
fluid inside the cell and the extracellular fluid outside it. Osmotic pressure occurs
when solutes are more concentrated on one side of the membrane than on the
other.
If you eat something salty, sodium ions spread through the blood and the
extracellular fluid but do not cross the membranes into cells. The result is a higher
concentration of solutes outside the cells than inside, and the resulting osmotic
pressure draws water from the cells into the extracellular fluid. Certain neurons
detect their own loss of water and then trigger osmotic thirst, which helps restore
the normal state. The kidneys also excrete more concentrated urine to rid the body
of excess sodium and maintain as much water as possible.

How does the brain detect osmotic pressure?

Of all brain areas, those around the third ventricle have the leakiest blood-brain
barrier. A weak blood-brain barrier would be harmful for most neurons, but it
helps cells monitor the contents of the blood. The areas important for detecting
osmotic pressure and the salt content of the blood include the OVLT (organum
vasculosum laminae terminalis) and the subfornical organ (SFO).
The brain also gets information
from receptors in the stomach that
detect high levels of sodium,
enabling the brain to anticipate an
osmotic need before the rest of the
body actually experiences it.
Receptors in the OVLT, the
subfornical organ, the stomach,
and elsewhere relay their
information to several parts of the
hypothalamus, including the
supraoptic nucleus and the
paraventricular nucleus (PVN),
which control the rate at which the
posterior pituitary releases
vasopressin. Receptors also relay
information to the lateral preoptic area and surrounding parts of the
hypothalamus, which control drinking.

How do you know when to stop drinking?

You do not wait until water has restored normal osmotic pressure for the receptors
in the brain. The water you drink has to be absorbed through the digestive system
and then pumped through the blood to the brain. That process takes 15 minutes
or so, and if you continued drinking for that long, you would drink far more than
you need. The body monitors swallowing and detects the distension of the stomach
and upper part of the small intestine. Those messages limit drinking to not much
more than you need at a given time.

HYPOVOLEMIC THIRST & SODIUM SPECIFIC HUNGER

Suppose you lose a significant amount of body fluid by bleeding, diarrhea, or
sweating. Although osmotic pressure has not changed anywhere in your body, you
need fluid. Your heart has trouble pumping blood up to the head, and nutrients do
not flow as easily as usual into your cells. Your body will react with hormones that
constrict blood vessels—vasopressin and angiotensin II. When blood volume drops,
the kidneys release the enzyme renin, which splits a portion off angiotensinogen, a
large protein in the blood, to form angiotensin I, which other enzymes convert to
angiotensin II. Like vasopressin, angiotensin II constricts the blood vessels,
compensating for the drop in blood pressure.
Angiotensin II also helps trigger thirst in conjunction with receptors that detect
blood pressure in the large veins. However, this thirst is different from osmotic
thirst because you need to restore lost salts and not just water. This kind of thirst
is known as hypovolemic (HI-po-vo-LEE-mik) thirst, meaning thirst based on low
volume. When angiotensin II reaches the brain, it stimulates neurons in areas
adjoining the third ventricle.
Those neurons send axons to the hypothalamus, where they release angiotensin II
as their neurotransmitter. With hypovolemic thirst can’t drink much water without
diluting its body fluids and changing their osmotic pressure. The animal therefore
increases its preference for slightly salty water.
Angiotensin II has several physiological effects: It stimulates the secretion of
hormones by the posterior pituitary gland and the adrenal cortex that cause the
kidneys to conserve water and sodium, and it increases blood pressure by causing
muscles in the small arteries to contract. In addition, AII has two behavioural effects:
It initiates both drinking and a salt appetite. Therefore, a reduction in the flow of
blood to the kidneys causes water and sodium to be retained by the body, helps to
compensate for their loss by reducing the size of the blood vessels, and encourages
the animal to find and ingest both water and salt.

If the animal is offered both water and salt, it alternates between them to yield an
appropriate mixture. It shows a strong craving for salty tastes. This preference,
known as sodium-specific hunger, develops automatically as soon as the need exists.
You may have noticed this phenomenon yourself. A woman around the time of
menstruation, or anyone who has sweated heavily, finds that salty snacks taste
especially good.
Sodium-specific hunger depends partly on hormones. When the body’s sodium
reserves are low, the adrenal glands produce the hormone aldosterone, which causes
the kidneys, salivary glands, and sweat glands to retain salt. Aldosterone and
angiotensin II together change the properties of taste receptors on the tongue,
neurons in the nucleus of the tractus solitarius (part of the taste system), and
neurons elsewhere in the brain to increase salt intake.

NEURAL MECHANISMS OF THIRST

As you have already learned, the osmoreceptors that initiate drinking are located
in the OVLT and SFO. The lamina terminalis seems to be the part of the brain
where osmometric and volumetric signals are integrated to control drinking. The
signal for volumetric thirst is provided by angiotensin II. Because this peptide does
not cross the blood–brain barrier, it cannot directly affect neurons in the brain
except for those located in one of the circumventricular organs. In fact, research
indicates that the subfornical organ is the site at which blood angiotensin acts to
produce thirst. This structure gets its name from its location, just below the
commissure of the ventral fornix.
The median preoptic nucleus receives information from angiotensin-sensitive
neurons in the SFO. In addition, this nucleus receives information from the OVLT
(which contains osmoreceptors) and from the nucleus of the solitary tract (which
receives information from the atrial baroreceptors). Excitotoxic lesions of the
median preoptic nucleus, which destroy cell bodies but spare axons passing through
the structure, cause severe deficits in osmometric thirst.
The median preoptic nucleus integrates the information it receives and, through its
efferent connections with other parts of the brain, controls drinking.
The region of the lamina terminalis seems to play a critical role in fluid regulation
in humans as well. Brain damage that includes this region can cause adipsia—lack
of drinking. The patients report no sensation of thirst even after they are given an
injection of hypertonic saline. To survive, they must deliberately drink water at
regular intervals each day, even though they feel no need to do so.
SEX

Reproductive behaviors constitute the most important category of social behaviors,

because without them, most species would not survive. These behaviors—which
include courting, mating, parental behavior, and most forms of aggressive
behaviors—are the most striking categories of sexually dimorphic behaviors, that is,
behaviors that differ in males and females (di + morphous, “two forms”).

Sexual Development

A person’s chromosomal sex is determined at the time of fertilization. However,

this event is merely the first in a series of steps that culminate in the development
of a male or female.

Production of Gametes and Fertilization

All cells of the human body (other than sperms or ova) contain twenty-three pairs
of chromosomes. The genetic information that programs the development of a
human is contained in the DNA that constitutes these chromosomes.
The production of gametes (ova and sperms; gamein means “to marry”) entails a
special form of cell division. This process produces cells that contain one member of
each of the twenty-three pairs of chromosomes. The development of a human
begins at the time of fertilization, when a single sperm and ovum join, sharing their
twenty-three single chromosomes to reconstitute the twenty-three pairs.
The last pair consists of two sex chromosomes, which contain genes that determine
whether the offspring will be a boy or a girl.
There are two types of sex chromosomes: X chromosomes and Y chromosomes.
Females have two X chromosomes (XX); thus, all the ova that a woman produces
will contain an X chromosome. Males have an X and a Y chromosome (XY). When
a man’s sex chromosomes divide, half the sperms contain an X chromosome, and
the other half contain a Y chromosome. A Y-bearing sperm produces an XY-
fertilized ovum and therefore a male. An X-bearing sperm produces an XXfertilized
ovum and therefore a female.

Development of the Sex Organs

Men and women differ in many ways: Their bodies are different, parts of their
brains are different, and their reproductive behaviors are different.
Exposure to sex hormones, both before and after birth, is responsible for our sexual
dimorphism. What the Y chromosome does control is the development of the glands
that produce the male sex hormones.

Gonads
There are three general categories of sex organs: the gonads, the internal sex organs,
and the external genitalia. The gonads—testes or ovaries—are the first to develop.
Gonads (from the Greek gonos, “procreation”) have a dual function: They produce
ova or sperms, and they secrete hormones. Through the sixth week of prenatal
development, male and female fetuses are identical. Both sexes have a pair of
identical undifferentiated gonads, which have the potential of developing into either
testes or ovaries. The factor that controls their development appears to be a single
gene on the Y chromosome called Sry (sex-determining region Y). This gene
produces a protein that binds to the DNA of cells in the undifferentiated gonads
and causes them to become testes. Testes are also known as testicles, Latin for
“little testes.”) Believe it or not, the words “testis” and “testify” have the same
root, meaning “witness.” If the Sry gene is not present, the undifferentiated gonads
become ovaries.
Once the gonads have developed, a series of events is set into action that determines
the individual’s gender. These events are directed by hormones, which affect sexual
development in two ways. During prenatal development these hormones have
organizational effects, which influence the development of a person’s sex organs and
brain.
The second role of sex hormones is their activational effect. These effects occur later
in life, after the sex organs have developed. For example, hormones activate the
production of sperms, make erection and ejaculation possible, and induce ovulation.
Because the bodies of adult males and females have been organized differently, sex
hormones will have different activational effects in the two sexes.

Internal Sex Organs

Early in embryonic development the internal sex organs are bisexual; that is, all
embryos contain the precursors for both female and male sex organs. However,
during the third month of gestation, only one of these precursors develops; the
other withers away. The precursor of the internal female sex organ, which develops
into the fimbriae and Fallopian tubes, the uterus, and the inner two-thirds of the
vagina, is called the Müllerian system. The precursor of the internal male sex organs,
which develops into the epididymis, vas deferens, and seminal vesicles, is called the
Wolffian system. The gender of the internal sex organs of a fetus is determined by
the presence or absence of hormones secreted by the testes. If these hormones are
present, the Wolffian system develops. If they are not, the Müllerian system
develops. The Müllerian (female) system needs no hormonal stimulus from the
gonads to develop; it just normally does so. (Turner’s syndrome, a disorder of sexual
development that I will discuss later, provides evidence for this assertion.) In
contrast, the cells of the Wolffian (male) system do not develop unless they are
stimulated to do so by a hormone. Thus, testes secrete two types of hormones. The
first, a peptide hormone called anti- Müllerian hormone, does exactly what its
name says: It prevents the Müllerian (female) system from developing. It therefore
has a defeminizing effect. The second, a set of steroid hormones called androgens,
stimulates the development of the Wolffian system. Androgens have a masculinizing
effect. Two different androgens are responsible for masculinization. The first,
testosterone, is secreted by the testes and gets its name from these glands. An
enzyme called 5a reductase converts some of the testosterone into another
androgen, known as dihydrotestosterone. The fact that the internal sex organs of
the human embryo are bisexual and could potentially develop as either male or
female is dramatically illustrated by two genetic disorders: androgen insensitivity
syndrome and persistent Müllerian duct syndrome. Some people are insensitive to
androgens; they have androgen insensitivity syndrome, one of the more aptly
named disorders.

External Genitalia
The external genitalia are the visible sex organs, including the penis and scrotum in
males and the labia, clitoris, and outer part of the vagina in females. In the presence
of dihydrotestosterone, the external genitalia will become male. Thus, the gender
of a person’s external genitalia is determined by the presence or absence of an
androgen, which explains why people with Turner’s syndrome have female external
genitalia even though they lack ovaries. People with androgen insensitivity
syndrome have female external genitalia too, because without androgen receptors
their cells cannot respond to the androgens produced by their testes.

Sexual Maturation
The primary sex characteristics include the gonads, internal sex organs, and
external genitalia. These organs are present at birth. The secondary sex
characteristics, such as enlarged breasts and widened hips or a beard and deep
voice, do not appear until puberty. However, at puberty the gonads are stimulated
to produce their hormones, and these hormones cause the person to mature
sexually. onset of puberty occurs when cells in the hypothalamus secrete
gonadotropin-releasing hormones (GnRH), which stimulate the production and
release of two gonadotropic hormones by the anterior pituitary gland. The
gonadotropic (“gonad-turning”) hormones stimulate the gonads to produce their
hormones, which are ultimately responsible for sexual maturation.
The two gonadotropic hormones are folliclestimulating hormone (FSH) and
luteinizing hormone (LH), named for the effects they produce in the female
(production of a follicle and its subsequent luteinization, However, the same
hormones are produced in the male, where they stimulate the testes to produce
sperms and to secrete testosterone. If male and female pituitary glands are
exchanged in rats, the ovaries and testes respond perfectly to the hormones
secreted by the new glands
The secretion of GnRH, which directs the production of the gonadotropic hormones,
which in turn stimulate puberty and production of the sex hormones secreted by
the gonads, is under the control of another peptide: kisspeptin. Kisspeptin, produced
by neurons in the arcuate nucleus of the hypothalamus, is essential for the initiation
of puberty and the maintenance of male and female reproductive ability. In
response to the gonadotropic hormones (usually called gonadotropins) the gonads
secrete steroid sex hormones. The ovaries produce estradiol, one of a class of
hormones known as estrogens.
The gonadal steroids affect many parts of the body. Both estradiol and androgens
initiate closure of the growing portions of the bones and thus halt skeletal
growth. In females, estradiol also causes breast development, growth of the lining
of the uterus, changes in the deposition of body fat, and maturation of the female
genitalia. In males, androgens stimulate growth of facial, axillary (underarm), and
pubic hair; lower the voice; alter the hairline on the head (often causing baldness
later in life); stimulate muscular development; and cause genital.

Hormonal Control of Sexual Behavior

Hormones have organizational and activational effects on the internal sex organs,
genitals, and secondary sex characteristics. Naturally, all of these effects influence
a person’s behavior.
Hormonal Control of Female Reproductive Cycles
The reproductive cycle of female primates is called a menstrual cycle (from mensis,
meaning “month”). The female reproductive cycle of most primates, including
humans; characterized by growth of the lining of the uterus, ovulation, development
of a corpus luteum, and (if pregnancy does not occur), menstruation. A cycle begins
with the secretion of gonadotropins by the anterior pituitary gland. These hormones
(especially FSH) stimulate the growth of ovarian follicles, small spheres of epithelial
cells surrounding each ovum. Women normally produce one ovarian follicle each
month; if two are produced and fertilized, dizygotic (fraternal) twins will develop.
As ovarian follicles mature, they secrete estradiol, which causes growth of the lining
of the uterus in preparation for implantation of the ovum, should it be fertilized
by a sperm. Feedback from the increasing level of estradiol eventually triggers the
release of a surge of LH by the anterior pituitary gland.
The LH surge causes ovulation: The ovarian follicle ruptures, releasing the ovum.
Under the continued influence of LH, the ruptured ovarian follicle becomes a corpus
luteum (“yellow body”), which produces estradiol and progesterone.
The latter hormone promotes pregnancy (gestation). It maintains the lining of the
uterus, and it inhibits the ovaries from producing another follicle. Meanwhile, the
ovum enters one of the Fallopian tubes and begins its progress toward the uterus.
If it meets sperm cells during its travel down the Fallopian tube and becomes
fertilized, it begins to divide, and several days later it attaches itself to the uterine
wall. If the ovum is not fertilized or if it is fertilized too late to develop sufficiently
by the time it gets to the uterus, the corpus luteum will stop producing estradiol
and progesterone, and then the lining of the walls of the uterus will slough off. At
this point, menstruation will commence.

Hormonal Control of Sexual Behavior of Laboratory Animals

Males
Male sexual behavior is quite varied, although the essential features of intromission
(entry of the penis into the female’s vagina), pelvic thrusting (rhythmic movement
of the hindquarters, causing genital friction), and ejaculation (discharge of semen)
are characteristic of all male mammals. Humans, of course, have invented all kinds
of copulatory and noncopulatory sexual behavior. For example, the pelvic
movements leading to ejaculation may be performed by the woman, and sex play
can lead to orgasm without intromission.
After ejaculating, the male refrains from sexual activity for a period of time
(minutes, in the rat). Most mammals will return to copulate several times, finally
showing a longer pause, called a refractory period. (The term comes from the Latin
refringere, “to break off.”) Sexual behavior of male rodents depends on testosterone,
a fact that has long been recognized (Bermant and Davidson, 1974). If a male rat
is castrated (that is, if his testes are removed), his sexual activity eventually ceases.
However, the behavior can be reinstated by injections of testosterone.
Other hormones play a role in male sexual behavior. Oxytocin is a hormone
produced by the posterior pituitary gland- released at the time of orgasm in both
males and females and appears to contribute to the contractions of the smooth
muscle in the male ejaculatory system and of the vagina and uterus.

Females
The mammalian female has been described as the passive participant in copulation.
It is true that in some species the female’s role during the act of copulation is merely
to assume a posture that exposes her genitals to the male. This behavior is called
the lordosis response (from the Greek lordos, meaning “bent backward”). Sexual
behavior of female rodents depends on the gonadal hormones present during estrus:
estradiol and progesterone.
Although sexual receptivity can be produced in ovariectomized rodents by
administering large doses of estradiol alone, the most effective treatment duplicates
the normal sequence of hormones: a small amount of estradiol, followed by
progesterone. Progesterone alone is ineffective; thus, the estradiol “primes” its
effectiveness. Priming with estradiol takes about 16–24 hours, after which an
injection of progesterone produces receptive behaviors within an hour. The sequence
of estradiol followed by progesterone has three effects on female rats: It increases
their receptivity, their proceptivity, and their attractiveness. Receptivity refers to
their ability and willingness to copulate— to accept the advances of a male by
holding still and displaying lordosis when he attempts to mount her. Proceptivity
refers to a female’s eagerness to copulate, as shown by the fact that she seeks out
a male and engages in behaviors that tend to arouse his sexual interest.
Attractiveness refers to physiological and behavioural changes that affect the male.
The male rat (along with many other male mammals) is most responsive to females
who are in estrus (“in heat”).
Organizational Effects of Androgens on Behavior: Masculinization and
Defeminization
The dictum “Nature’s impulse is to create a female” applies to sexual behavior as
well as to sex organs. That is, if a rodent’s brain is not exposed to androgens during
a critical period of development, the animal will engage in female sexual behavior
as an adult (if the animal is then given estradiol and progesterone). if a rodent
brain is exposed to androgens during development, two phenomena occur:
behavioural defeminization and behavioral masculinization. Behavioral
defeminization refers to the organizational effect of androgens that prevents the
animal from displaying female sexual behavior in adulthood. As we shall see later,
this effect is accomplished by suppressing the development of neural circuits
controlling female sexual behavior. For example, if a female rodent is ovariectomized
and given an injection of testosterone immediately after birth, she will not respond
to a male rat when, as an adult, she is given injections of estradiol and
progesterone. Behavioral masculinization refers to the organizational effect of
androgens that enables animals to engage in male sexual behavior in adulthood.
This effect is accomplished by stimulating the development of neural circuits
controlling male sexual behavior. For example, if the female rodent in my previous
example is given testosterone in adulthood rather than estradiol and progesterone,
she will mount and attempt to copulate with a receptive female.

Human Sexual Behavior

Activational Effects of Sex Hormones in Women
the sexual behavior of most female mammals other than higher primates is
controlled by the ovarian hormones estradiol and progesterone. the ovarian
hormones control not only the willingness (or even eagerness) of an estrous female
to mate but also her ability to mate. In higher primates (including our own species)
the ability to mate is not controlled by ovarian hormones. There are no physical
barriers to sexual intercourse during any part of the menstrual cycle. If a woman
or other female primate consents to sexual activity at any time (or is forced to
submit by a male), intercourse can certainly take place.
Although ovarian hormones do not control women’s sexual activity, they may still
have an influence on women’s sexual interest. Early studies reported that
fluctuations in the level of ovarian hormones had only a minor effect on women’s
sexual interest. Wallen (1990) notes, these studies have almost all involved married
women who live with their husbands. In stable, monogamous relationships in which
the partners are together on a daily basis, sexual activity can be instigated by either
of them. Normally, a husband does not force his wife to have intercourse with him,
but even if she is not interested in engaging in sexual activity at that moment, she
may find that she wants to do so because of her affection for him. Thus, changes
in sexual interest and arousability might not always be reflected in changes in sexual
behavior. In fact, a study of lesbian couples (whose menstrual cycles are likely to be
synchronized) found a significant increase in sexual interest and activity during the
middle portions of the women’s cycles (Matteo and Rissman, 1984), which suggests
that ovarian hormones do influence women’s sexual interest.
Men initiated sexual activity at about the same rate throughout the woman’s cycle,
whereas sexual activity initiated by women showed a distinct peak around the time
of ovulation, when estradiol levels are highest. Bullivant et al. (2004) found that
women were more likely to initiate sexual activity and were more likely to engage
in sexual fantasies just before and during the surge in luteinizing hormone that
stimulates ovulation. In particular, they become more attracted to male
characteristics that might indicate high genetic quality (or did so in the evolution
of our species). For example, Gangestad and Thornhill note that studies have shown
that at midcycle, women’s preference increases for the sight of facial and bodily
masculinity, for masculine behavioral displays, for masculine vocal qualities, for
androgen-related scents, and for body symmetry, which correlates with genetic
fitness.
Wallen (2001) points out that although ovarian hormones may affect a woman’s
sexual interest, her behaviour can be influenced by other factors as well. For
example, if a woman does not want to become pregnant and does not have absolute
confidence in her method of birth control, she may avoid sexual intercourse at
midcycle, around the time of ovulation—even if her potential sexual interest is at
a peak. In fact, Harvey (1987) found that women were more likely to engage in
autosexual activity at this time. On the other hand, women who want to become
pregnant are more likely to initiate sexual intercourse during the time when they
are most likely to conceive. Several studies suggest that women’s sexual interest can
be stimulated by androgens. There are two primary sources of androgens in the
female body: the ovaries and the adrenal glands. The primary ovarian sex steroids
are, of course, estradiol and progesterone, but these glands also produce
testosterone. The adrenal glands produce another androgen, androstenedione,
along with other adrenocortical steroids. However, the available evidence indicates
that androgens by themselves (in the absence of estradiol) do not directly stimulate
women’s sexual interest but appear to amplify the effects of estradiol.

Activational Effects of Sex Hormones in Men

men resemble other mammals in their behavioral responsiveness to testosterone.
With normal levels they can be potent and fertile; without testosterone, sperm
production ceases, and sooner or later, so does sexual potency.
The decline of sexual activity after castration isquite variable. As reported by Money
and Ehrhardt (1972), some men lose potency immediately, whereas others show
a slow, gradual decline over several years. Wallen and his colleagues (Wallen et al.,
1991; Wallen, 2001) injected a GnRH antagonist in seven adult male rhesus
monkeys that were part of a larger group. The injection suppressed testosterone
secretion, and sexual behavior declined after one week. However, the decline was
related to the animal’s social rank and sexual experience: More sexually experienced,
high-ranking males continued to copulate. In fact, the highest-ranking male
continued to copulate and ejaculate at the same rate as before, even though his
testosterone secretion was suppressed for almost eight weeks.

Neural Control of Sexual Behavior

Males
Spinal Mechanisms
Some sexual responses are controlled by neural circuits contained within the spinal
cord. Men with injuries that totally transect the spinal cord have become fathers
when their wives have been artificially inseminated with semen obtained by
mechanical stimulation.
Brackett et al. (1998) found that vibratory stimulation of the penis successfully
elicited ejaculation in most men with complete spinal cord transection above the
tenth thoracic segment, which suggests that the circuits in the spinal cord that
control the ejaculatory response are located below this region. Because the spinal
damage prevents sensory information from reaching the brain, these men are
unable to feel the stimulation and do not experience an orgasm.
Ejaculation occurs after sufficient amount of tactile stimulation of an erect penis
causes activation of the spinal ejaculation generator. Coolen and her colleagues have
identified a group of neurons in the lumbar region of the rat spinal cord that
appear to constitute a critical part of the spinal ejaculation generator. These
neurons project to adjacent neurons in the spinal cord that control the sympathetic
and parasympathetic mechanisms that result in emission and ejaculation of semen.
They also project to a nucleus in a specific part of the posterior intralaminar
thalamus, so the investigators refer to them as lumbar spinothalamic (LSt) cells.
This projection presumably provides input to the brain that constitutes part of the
pleasurable orgasmic sensation. Specific destruction of these neurons with a toxin
completely abolishes ejaculation but does not impair the animal’s ability to produce
an erection, mount an estrous female, and achieve intromission.

Brain Mechanisms

brain mechanisms have both excitatory and inhibitory control of these circuits.
Although tactile stimulation of a man’s genitals can stimulate erection and
ejaculation, these responses can be inhibited by the context.
In addition, a man’s penis can become erect when he sees his partner or has erotic
thoughts—even when his penis is not being touched. Thus, there must be brain
mechanisms that can activate or suppress the spinal mechanisms that control
genital reflexes.
The medial preoptic area (MPA), located just rostral to the hypothalamus, is the
forebrain region most critical for male sexual behavior. (As we will see later in this
chapter, it is also critical for other sexually dimorphic behavior, including maternal
behavior.) Electrical stimulation of this region elicits male copulatory behavior
(Malsbury, 1971), and sexual activity increases the firing rate of single neurons in
the MPA.
Domingues, Gil, and Hull (2006) found that mating increased the release of
glutamate in the MPA and that infusion of glutamate into the MPA
increased the frequency of ejaculation. Finally, destruction
of the MPA abolishes male sexual behaviour.

The organizational effects of androgens are responsible

for sexual dimorphisms in brain structure. Gorski et
al. (1978) discovered a nucleus within the MPA of the rat
that is three to seven times larger in males than in females.
This area is called (appropriately enough) the sexually dimorphic nucleus (SDN) of
the preoptic area.
(As we saw in the previous discussion of brain mechanisms
of gender identity, this brain region, which is called
the uncinate nucleus in humans, is sexually dimorphic in
our species as well.) The size of this nucleus is controlled
by the amount of androgens present during fetal development.
According to Rhees, Shryne, and Gorski (1990a,
1990b), the critical period for masculinization of the
SDN appears to start on the eighteenth day of gestation
and end once the animals are five days old. (Normally,
rats are born on the twenty-second day of gestation.) De
Jonge et al. (1989) found that lesions of the SDN decrease
masculine sexual behavior. (See Figure 10.14.)
Androgens also exert their activational effects on neurons
in the MPA and associated brain regions. If a male
rodent is castrated in adulthood, its sexual behavior will
cease. However, the behavior can be reinstated by implanting
a small amount of testosterone directly into the MPA
or in two regions whose axons project to the MPA: the
central tegmental field and the medial amygdala (Sipos
and Nyby, 1996; Coolen and Wood, 1999). Both of these
regions contain a high concentration of androgen receptors
in the male rat brain.

the primary and

accessory olfactory systems play important roles in reproductive
behavior. Both of these systems send axons
to the medial nucleus of the amygdala, which in turn
sends axons to the MPA.

Both of these systems send axons

to the medial nucleus of the amygdala, which in turn
sends axons to the MPA.

lesions of the medial amygdala abolished the

sexual behavior of male rodents, presumably because
the lesions disrupted the activating effects of pheromones
on the MPA.

The MPA also receives somatosensory

information from the genitals through connections with
the central tegmental field of the midbrain and the
medial amygdala. The act of copulation activates neurons
in both of these regions.

Anatomical tracing studies suggest that the most

important connections between the MPA and the spinal
ejaculation generator are accomplished through the
periaqueductal gray matter (PAG) of the midbrain and
the nucleus paragigantocellularis (nPGi) of the medulla.

The nPGi normally inhibits spinal cord sexual

reflexes, so one of the tasks of the pathway originating
in the MPA is to suppress this inhibition. The MPA suppresses
the nPGi directly through an inhibitory pathway
and does so indirectly by inhibiting the activity of the
PAG, which normally excites the nPGi.

application of serotonin (5-HT) to the spinal

cord suppresses ejaculation. This connection may explain
a well-known side effect of specific serotonin
reuptake inhibitors (SSRIs). Men who take SSRIs as a
treatment for depression often report that they have no
trouble attaining an erection but have difficulty achieving
an ejaculation. Presumably, the action of the drug
as an agonist at the serotonergic synapses in the spinal
cord increases the inhibitory influence of nPGi on the
spinal ejaculation generator.

A functional-imaging study by Holstege et al.

(2003b) examined the pattern of brain activation during
ejaculation in men that was elicited by the men’s
female partners by means of manual stimulation. Ejaculation
was accompanied by neural activity in many brain
regions, including the junction between the midbrain and the diencephalon, which
includes the ventral tegmental
area (probably involved in the pleasurable, reinforcing
effects of orgasm), other midbrain regions, several
thalamic nuclei, the lateral putamen (part of the
basal ganglia), and the cerebellum. Decreased activity was
seen in the amygdala and the nearby entorhinal cortex.

the amygdala is involved in

defensive behavior and in negative emotions such as
fear and anxiety—and these emotions certainly interfere
with erection and ejaculation. Decreased activation
is also seen in this structure when people who are deeply
in love see pictures of their loved one.

Females

another region in the ventral forebrain plays a similar

role in female sexual behavior: the ventromedial
nucleus of the hypothalamus (VMH). A female rat with
bilateral lesions of the ventromedial nuclei will not display
lordosis, even if she is treated with estradiol and
progesterone. Conversely, electrical stimulation of the
ventromedial nucleus facilitates female sexual behaviour.

the medial amygdala

of males receives chemosensory information from
the vomeronasal system and somatosensory information
from the genitals, and it sends efferent axons to the
medial preoptic area. These connections are found in
females as well. In addition, neurons in the medial
amygdala also send efferent axons to the VMH. In fact,
copulation or mechanical stimulation of the genitals or
flanks of a female rat increases the activation of neurons
in both the medial amygdala and the VMH.
The estrogen sets the stage, so to speak,
and the progesterone stimulates the sexual behavior.
Injections of these hormones directly into the VMH will
stimulate sexual behavior even in females whose ovaries
have been removed.

And if a chemical that blocks the

production of progesterone receptors is injected into
the VMH, the animal’s sexual behavior is disrupted
(Ogawa et al., 1994). Thus, estradiol and progesterone
exert their effects on female sexual behavior by activating
neurons in this nucleus.

The mechanism by which estradiol primes a female’s

sensitivity to progesterone appears to be simple:
Estradiol increases the production of progesterone
receptors, which greatly increases the effectiveness of
progesterone.

The neurons of the ventromedial nucleus send axons

to the periaqueductal gray matter. This region, too,
has been implicated in female sexual behaviour

electrical stimulation
of the PAG facilitates lordosis in female.

estradiol treatment
or electrical stimulation of the ventromedial nuclei increased
the firing rate of neurons in the PAG. (The PAG
contains both estrogen and progesterone receptors.)

A functional-imaging study by Holstege et al. (2003a)

investigated the neural activation that accompanies
orgasm in women, elicited by manual clitoral stimulation
supplied by the women’s male partners. They observed
activation in the junction between the midbrain
and diencephalon, the lateral putamen, and the cerebellum,
just as was observed in men.

They also saw activation in the PAG, a critical region for

copulatory behavior in female laboratory animals.

Formation of Pair Bonds

In approximately 5 percent of mammalian species, heterosexual
couples form monogamous, long-lasting bonds.
In humans, such bonds can be formed between members
of homosexual couples as well. As naturalists and anthropologists
have pointed out, monogamy is not always exclusive.

n many species of animals, humans included, individuals sometimes cheat on their

partners. In addition,
some people display serial monogamy—intense relationships
that last for a period of time, only to be replaced
with similarly intense relationships with new partners.
And, of course, some cultures condone (or even encourage)
polygamy.

Many investigators believe that oxytocin and vasopressin

may play a role in the formation of pair
bonding in humans. For example, after intercourse,
at a time when blood levels of oxytocin are increased,
people report feelings of calmness and well-being,
which are certainly compatible with the formation of
bonds with one’s partner. However, it is difficult to
envision ways to perform definitive research on this
topic.

However, Heinrichs et al. (2003) found

that injections of oxytocin caused relaxation and a
reduction of anxiety in human subjects. In addition,
Kosfeld et al. (2005) found that oxytocin increased
trust.