Previous reports from this laboratory have described an ability of iontophoretically applied dopamine to attenuate the inhibitory effects of iontophoresed GABA on neurons of the substantia nigra pars reticulata. This finding raised the question of whether endogenous dopamine, released from dendrites of neighboring pars compacta dopamine neurons, might act as a neuromodulator which diminishes the inhibition of pars reticulata neurons evoked by either GABA iontophoresis or electrical stimulation of the striatonigral GABAergic pathway. Extracellular, single-unit activity of pars reticulata neurons was recorded in male rats anesthetized with chloral hydrate. In one set of studies, d-amphetamine, a drug reported to release dopamine from nigral dendrites, was administered intravenously (1.6 mg/kg) during regular, intermittent iontophoretic pulses of GABA. As had been previously observed with iontophoresed dopamine, i.v. amphetamine significantly lessened the inhibition of reticulata neurons produced by GABA application. This change was reflected by a decrease in GABA's inhibitory potency by 22% relative to the control level of inhibition achieved prior to amphetamine administration. Amphetamine caused no decreases in GABA's effectiveness, however, in animals that had previously received treatments that depleted or destroyed nigral dopamine stores, i.e., in rats pretreated with reserpine and alpha- methyl-p-tyrosine, or in rats with 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway. In a second set of experiments, amphetamine or dopamine was delivered iontophoretically while monitoring the GABA-mediated (bicuculline-reversible) inhibition of reticulata neurons that can be elicited by striatal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous single-unit recording studies have revealed that randomly selected pars reticulata neurons respond in a highly variable and complex fashion to intravenous administration of the dopamine agonist, apomorphine. The current studies were undertaken (1) to assess whether the variable pattern of responses of reticulata neurons to intravenous apomorphine correlates with their sites of projection and (2) to determine how reticulata responses to apomorphine might be altered by the presence of striatal dopaminergic supersensitivity. Extracellular, single-unit recording studies were conducted in anesthetized, paralyzed rats. Pars reticulata neurons were identified by antidromic activation from either the ventromedial nucleus of the thalamus or superior colliculus. Neurons of both subpopulations exhibited similar, highly variable changes in firing rate during the 10-min period immediately following intravenous injection of 320 micrograms/kg of apomorphine, a dose of the drug considered sufficient to stimulate striatal postsynaptic dopamine receptors. These responses, which were not qualitatively different from those previously observed among reticulata cells not distinguished on the basis of projection site, could be reversed by subsequent administration of dopamine antagonist drugs. In contrast to the variable responses in normal animals, the same dose of apomorphine caused a rapid and usually total inhibition of pars reticulata cell firing in rats which received 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway 6 to 8 weeks prior to recording experiments. These inhibitions of firing could also be reversed by administration of dopamine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)