Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons.

The electrophysiological responsiveness of nigrostriatal dopamine (DA) neurons to dorsal raphe stimulation and to systemic administration of serotonin (5-HT) selective compounds was examined in chloral hydrate-anesthetized rats. Electrical stimulation of the dorsal raphe selectively inhibited the firing rate of slowly firing (less than 4 spikes/sec) DA neurons. The 5-HT-1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine preferentially increased the firing rate of slowly firing DA neurons, but did not alter the responsiveness of these cells to quinpirole-induced inhibition of firing rate. This increase in firing rate was not observed following depletion of brain 5-HT by the neurotoxin 5,7-dihydroxytryptamine. The 5-HT-1B agonists trifluoromethylphenylpiperazine and M-chlorophenylpiperazine had only weak inhibitory effects on the firing rates of DA neurons, and also failed to alter the responsiveness of DA neurons to quinpirole-induced inhibition. Depletion of brain 5-HT (greater than 80%) by either para-chlorophenylalanine or 5,7-dihydroxytryptamine eliminated the rate-dependent nature of quinpirole-induced inhibition of nigrostriatal DA neurons, while having limited effects on the basal electrophysiological activity of these cells. These data suggest that 5-HT systems exert subtle influences on the activity and pharmacological responsiveness of nigrostriatal DA neurons.