Dopamine

Dopamine belongs to a family of biological compounds called catecholamines (see Figure 1). Dopamine is synthesized from the compound L-dihydroxyphenylalanine (L-dopa) via the enzyme dopa decarboxylase. In noradrenergic neurons and in the adrenal glands, dopamine is the precursor for the neurotransmitter norepinephrine. In dopaminergic neurons, dopamine itself acts as a neurotransmitter. Although dopaminergic neurons are not as widely distributed in the brain as noradrenergic neurons, they act to coordinate movement, to control the secretion of some hormones, and to regulate mood and emotional stability.

Dopamine's role in the coordination of movement can be partially understood by examining Parkinson's disease. This illness is associated with low levels of dopamine in the brain and is characterized by spastic motion of the eyelids as well as rhythmic tremors of the hands and other parts of the body. One method of treating Parkinson's disease is to increase the concentration of dopamine in the brain. This is most effectively accomplished by administering the precursor of dopamine, L-dopa. In order to prevent concentrations of norepinephrine from increasing as well, L-dopa is given in conjunction with a drug that inhibits norepinephrine synthesis .

The role that dopamine plays in regulating mood and emotional stability can be at least partially grasped by examining dopamine's role in schizophrenia and drug addiction. Schizophrenia is a disorder characterized by delusions, hallucinations, withdrawal from external reality, and emotional unresponsiveness. The dopamine theory of schizophrenia, proposed in 1965, attributes the disorder to elevated brain concentrations of dopamine or to a hypersensitivity of dopaminergic receptors , especially the D₂ and D₄ receptor subtypes. Several drugs used to treat schizophrenic patients bind to D₂ and D₄ receptors and block the dopaminergic response.

Dopamine is also an important component of the brain's "reward system" and is believed to play a role in drug addiction. Increased levels of dopamine have been associated with cocaine, amphetamine , and marijuana use, as well as alcohol and nicotine addiction.

see also Neurotransmitters.

Jennifer L. Powers

Bibliography

Balter, Michael (1996). "New Clues to Brain Dopamine Control, Cocaine Addiction." Science 271:909.

Internet Resources

Indiana University School of Medicine, Terre Haute Center for Medical Education. The Medical Biochemistry Page. "Biochemistry of Nerve Transmission." Available from <http://web.indstate.edu/thcme/mwking/nerves.html>.

Northeastern University, Physical Therapy Department. Neuroanatomy Cyberlectures. "Pharmacology: The Chemistry of the Nervous System." Available from <http://www.ptd.neu.edu/neuroanatomy/cyberclass/Pharmacology>.

dopamine (doh-pă-meen) n. a catecholamine derived from dopa that functions as a neurotransmitter, acting on specific dopamine receptors and also on adrenergic receptors throughout the body; it also stimulates the release of noradrenaline from nerve endings. Dopamine is used as a drug to increase the strength of contraction of the heart in heart failure, shock, severe trauma, and septicaemia. It is administered by injection in carefully controlled dosage.

dopamine is a catecholamine, from which other important catecholamines (adrenaline and noradrenaline) are derived, but it is also an important neurotransmitter in its own right, especially in the brain. Of particular importance are central nervous pathways involved with the co-ordination of movement and with behaviour and emotion. As with the other catecholamines, dopamine is released from nerve endings where it acts upon receptors on other nerve cells to produce its effects. There are two sorts of receptors for dopamine, namely D₁ and D₂, of which the second are of greater importance. After release the dopamine is rapidly destroyed or taken up back into the nerve fibres for reuse. A number of medical conditions are associated with under-activity or over-activity of dopamine pathways in the brain. The rigidity and tremor, together with the hypokinesia (relative lack of voluntary movement), of Parkinson's disease are associated with lack of dopaminergic function in the nigrostriatal pathway in the brain. One form of treatment for this disease is to give large amounts of L-DOPA, the precurser of dopamine, so that some reaches the brain, is converted to dopamine, and restores some lost functions. Another approach is to transplant fetal dopamine-secreting cells into the relevant brain nuclei to take over the function of the diseased nerve cells. Over-activity of dopaminergic nerves, especially in the limbic system, is associated with schizophrenia. It has also been claimed that individuals with mutations affecting the dopamine D₂ receptors show enhanced risk-taking behaviour. Some drugs, like the amphetamines, release dopamine from nerve endings in the brain, leading to hyperactivity and manic behaviour. Dopamine pathways are also associated with the vomiting centre in the brain, so drugs which block the dopamine receptors, such as the phenothiazines, have a calming effect on schizophrenics and are also useful anti-emetic drugs. There are a few dopamine pathways in other parts of the body, for example the kidney, where activation causes vasodilation. Dopamine increases the force of contraction of the heart and an infusion is sometimes used to treat shock resulting from blood loss.

Alan W. Cuthbert