Effects of para-chlorophenylalanine on amphetamine and haloperidol-induced changes in striatal dopamine turnover.

Para-chlorophenylalanine (PCPA) was administered to rats, and the animals were sacrificed 48 h later. Animals received various doses of S(+)-amphetamine (AMPH) 31 min before sacrifice or of haloperidol (HAL) 46 min before sacrifice and an intracerebral injection of [3H]tyrosine 15 min prior to sacrifice. PCPA pretreatment potentiated the increased accumulation of striatal [3H]dopamine (DA) induced by doses of AMPH to 1.5 mg/kg, and inhibited the decrease in striatal [3H]DA accumulation observed at higher doses (greater than 2.5 mg/kg) of AMPH. Further, the AMPH-induced increase in endogenous levels of striatal DA was inhibited by PCPA pretreatment. Similarly, PCPA pretreatment potentiated the HAL-induced increase in striatal [3H]DA accumulation. The data are discussed with respect to an inhibitory serotonergic influence on nigrostriatal DA function, and the relationship of nigrostriatal biochemical events to AMPH-induced behavioral changes.