Apparent serotonergic modulation of the dose-dependent biphasic response of neostriatal neurons produced by d-amphetamine

Previous reports indicate that amphetamine produces a dose-dependent shift in the firing rate of neurons in the anterior neostriatum that parallels the shift in behavior from locomotion to focused stereotypy. To determine if para-chlorophenylalanine (PCPA), which alters the pattern of the behavioral response to amphetamine, also changes the pattern of the neuronal response to the drug, a dose-response analysis was performed on amphetamine-induced changes in unit activity in the anterior neostriatum of rats pretreated 48 h previously with 300 mg/kg PCPA or vehicle. An intraperitoneal injection of 1.0 mg/kg d-amphetamine, which inhibited neostriatal activity in vehicle controls, produced in PCPA-pretreated animals a prolonged excitation. In contrast, the pronounced increase in firing rate produced by 7.5 mg/kg d-amphetamine in control rats was significantly reduced following PCPA pretreatment. Liquid chromatograhy with electrochemical detection revealed that compared to controls, PCPA produced a significant reduction of serotonin, but not dopamine or norepinephrine, in the telencephalon. The differential effects of PCPA on the action of low and high doses of d-amphetamine in the anterior neostriatum may explain the differential influence of serotonergic systems on amphetamine-induced locomotion and stereotypy.