DOPAMINE FUNCTION

By Dr Ananya Mandal, MD

Dopamine is a neurotransmitter released by the brain that plays a number of roles in humans and other
animals. Some of its notable functions are in:

movement

memory

pleasurable reward

behavior and cognition

attention

inhibition of prolactin production

sleep

mood

learning

Excess and deficiency of this vital chemical is the cause of several disease conditions. Parkinson's disease
and drug addiction are some of the examples of problems associated with abnormal dopamine levels.

Where is dopamine produced?

Dopamine is produced in the dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain, the
substantia nigra pars compacta, and the arcuate nucleus of the hypothalamus.

Dopamine in movement

A part of the brain called the basal ganglia regulates movement. Basal ganglia in turn depend on a certain
amount of dopamine to function at peak efficiency. The action of dopamine occurs via dopamine receptors,
D1-5.

Dopamine reduces the influence of the indirect pathway, and increases the actions of the direct pathway
within the basal ganglia. When there is a deficiency in dopamine in the brain, movements may become
delayed and uncoordinated. On the flip side, if there is an excess of dopamine, the brain causes the body to
make unnecessary movements, such as repetitive tics.

Dopamine in pleasure reward seeking behavior

Dopamine is the chemical that mediates pleasure in the brain. It is released during pleasurable situations
and stimulates one to seek out the pleasurable activity or occupation. This means food, sex, and several
drugs of abuse are also stimulants of dopamine release in the brain, particularly in areas such as the nucleus
accumbens and prefrontal cortex.

Dopamine and addiction

Cocaine and amphetamines inhibit the re-uptake of dopamine. Cocaine is a dopamine transporter blocker
that competitively inhibits dopamine uptake to increase the presence of dopamine.

Amphetamine increases the concentration of dopamine in the synaptic gap, but by a different mechanism.
Amphetamines are similar in structure to dopamine, and so can enter the presynaptic neuron via its
dopamine transporters. By entering, amphetamines force dopamine molecules out of their storage vesicles.
By increasing presence of dopamine both these lead to increased pleasurable feelings and addiction.

Dopamine in memory

Levels of dopamine in the brain, especially the prefrontal cortex, help in improved working memory.
However, this is a delicate balance and as levels increase or decrease to abnormal levels, memory suffers.

Dopamine in attention

Dopamine helps in focus and attention. Vision helps a dopamine response in the brain and this in turn helps
one to focus and direct their attention. Dopamine may be responsible for determining what stays in the
short term memory based on an imagined response to certain information. Reduced dopamine
concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder.

Dopamine in cognition
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Dopamine in the frontal lobes of the brain controls the flow of information from other areas of the brain.
Disorders of dopamine in this region lead to decline in neurocognitive functions, especially memory,
attention, and problem-solving.

D1 receptors and D4 receptors are responsible for the cognitive-enhancing effects of dopamine. Some of the
antipsychotic medications used in conditions like schizophrenia act as dopamine antagonists. Older, so-called
"typical" antipsychotics most commonly act on D2 receptors, while the atypical drugs also act on D1, D3 and
D4 receptors.

Regulating prolactin secretion

Dopamine is the main neuroendocrine inhibitor of the secretion of prolactin from the anterior pituitary gland.
Dopamine produced by neurons in the arcuate nucleus of the hypothalamus is released in the hypothalamo-
hypophysial blood vessels of the median eminence, which supply the pituitary gland. This acts on the
lactotrope cells that produce prolactin. These cells can produce prolactin in absence of dopamine. Dopamine
is occasionally called prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone(PIH), or prolactostatin.

Social functioning

Low D2 receptor-binding is found in people with social anxiety or social phobia. Some features of negative
schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a low dopaminergic state
in certain areas of the brain.

On the other hand those with bipolar disorder in manic states become hypersocial, as well as hypersexual.
This is credited to an increase in dopamine. Mania can be reduced by dopamine-blocking anti-psychotics.

Dopamine levels and psychosis

Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia. Both the typical
and the atypical antipsychotics work largely by inhibiting dopamine at the receptor level.

Pain processing

Dopamine plays a role in pain processing in multiple levels of the central nervous system. This includes the
spinal cord, periaqueductal gray (PAG), thalamus, basal ganglia, insular cortex, and cingulate cortex. Low
levels of dopamine are associated with painful symptoms that frequently occur in Parkinson's disease.

Dopamine in nausea and vomiting

Dopamine is one of the neurotransmitters implicated in the control of nausea and vomiting via interactions
in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist and prevents nausea and
vomiting.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Sources

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3. http://psych.colorado.edu/~oreilly/papers/frankoreilly06.pdf

4. tauruspet.med.yale.edu/.../GJ-Wang-Lancet-2001-obesity.pdf

5. dionysus.psych.wisc.edu/.../BerridgeK2007a.pdf
6. www.uni-ulm.de/.../nrn_may2008_research_highlight.pdf

7. http://128.196.98.170/pubs/Dopamine-HBTNN2e-preprint.pdf