Dopamine autoreceptors: Distribution, role in neuronal activity and relation to antipsychotic drugs

Dopamine neurons of the central nervous system comprise the putative substrate for several neurological and psychiatric disorders. A notable feature of these neurons is their responsiveness to dopamine itself, mediated through autoreceptors located on the somadendritic regions and the terminals. Single-unit electrophysiological recording was employed to determine the operational characteristics of autoreceptors in populations of mesocortical dopaminergic neurons, and to compare the role of autoreceptors with other intrinsic and extrinsic mechanisms in the control of dopamine neuronal activity. It was found that autoreceptors at both the somadendritic and terminal regions physiologically regulate mesocortical dopaminergic neurons. These neurons had been previously proposed to be devoid of autoreceptors.; Autoreceptor stimulation participates in the post-action potential inhibition of dopaminergic neurons in concert with other intrinsic mechanisms, likely the spike-dependent afterhyperpolarization. Afferent input was found to control the pattern of dopamine impulse activity in a novel manner: prefrontal cortex stimulation elicited bursting activity in a subpopulation of mesencephalic dopaminergic neurons. This is the first afferent input known to evoke bursts in dopamine neurons.; The effects of chronic neuroleptic administration on dopaminergic and non-dopaminergic neurons of the midbrain were examined with behavioral, histological and electrophysiological methods. Rats treated with haloperidol for up to 14 months and withdrawn for two weeks exhibited perioral dyskinesias overtly similar to tardive dyskinesia in humans. The most striking electrophysiological finding was a decrease in firing rate of non-dopaminergic neurons of the substantia nigra pars reticulata. As these neurons comprise inhibitory basal ganglia output to a variety of motor centers, their decreased impulse flow following chronic haloperidol administration may disinhibit brainstem and thalamic regions involved in expression of dyskinesias.; The electrophysiology and pharmacology of acute and chronic neuroleptic drugs are combined in a theoretical framework that describes how neuropeptides colocalized within dopaminergic neurons might respond to neuroleptic administration.