Pharmacological Reviews, Vol 18, 925-964, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

DOPAMINE (3-HYDROXYTYRAMINE) AND BRAIN FUNCTION

¹ Department of Pharmacology, University of Vienna, Vienna, Austria

The whole body of evidence discussed in this article shows that brain dopamine can be regarded as a strong candidate for a physiologically active substance, regulating the functioning of some extrapyramidal centers, especially substantia nigra, striatum and pallidum. The following findings provide strong support for this view: The dopamine is mainly confined to the extrapyramidal regions mentioned; in these regions, the amine is localized in specific neurons and nerve terminals; its rate of turnover is of a high order of magnitude; is there a correlation between itsconcentration in the brain and the functional state of the extrapyramidal centers following administration of certain drugs; there is a striking relationship between some extrapyramidal disorders (drug-induced and genuine parkinsonism) and the lack of the amine in the substantia nigra, the striatum and the pallidum; and, finally, that substantia nigra exerts a direct influence on the concentration of the amine in the striatum by virtue of the nigro-striatal dopamine-containing fibers.

In the extrapyramidal centers, dopamine may have either inhibitory or excitatory activity. Neurophysiological evidence obtained in different species points to a predominantly inhibitory activity of dopamine on single neurons of the brain.

Evidence showing that in the retina and in the median eminence (including the pituitary stalk) dopamine may be the predominant catecholamine argues in favor of a specific function of the amine in these brain structures, although there are at present no direct findings to prove this suggestion.

From the evidence discussed in this article a good case can be made for the concept that the physiological activity of the brain dopamine is quite different from that of brain norepinephrine. There are as yet., however, no experiments to positively show that dopamine is a true neuro-transmitter substance in the brain. All central dopamine effects could equally well be explained by assuming that the amine is a modifier of synaptic transmission.

Therefore, in order to establish dopamine unequivocally as a central neurotransmitter substance, there is still one crucial experiment to be done: to demonstrate that upon stimulation of the relevant parts of the brain, dopamine is in fact released at synapses to exert by itself an effect on the neurons standing in synaptic relationship with the stimulated dopamine-containing terminals. It is to be hoped that we shall not have to wait too long for this experiment to be performed.

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