Differential effects of chronic treatment with chlorpromazine versus cocaine on behavioral responsiveness to nigral GABA receptor stimulation.

We examined whether any locus postsynaptic to the GABAergic striatonigral projection might be involved in the enhancement of behavioral response to dopaminergic stimulants induced by chronic treatment with either neuroleptic drugs or stimulants. Rats exposed chronically to either chlorpromazine or cocaine were tested for behavioral responses to bilateral intranigral microinfusions of muscimol (2.5 ng bilaterally). Chronic chlorpromazine-treated rats responded with more intense stereotypy to nigral muscimol than controls, but chronic cocaine-treated rats were less responsive than controls to intranigral muscimol. It therefore appears that changes in the responsiveness of neural outputs from, or distal to, substantia nigra may contribute to the enhanced behavioral effects of dopaminergic stimulants caused by chronic exposure to dopaminergic antagonists, but that the critical neural changes responsible for cocaine sensitization probably do not occur at, or distal to, the nigral outflow from the basal ganglia. At least at the nigral level, different neural mechanisms evidently mediate the increased stereotypy response to dopaminergic stimulation induced by chronic administration of either neuroleptic or stimulant drugs.