alpha-Methyl-p-tyrosine partially attenuates p-chloroamphetamine-induced 5-hydroxytryptamine depletions in the rat brain.

alpha-Methyl-p-tyrosine (AMT) partially attenuates the long-term p-chloroamphetamine (pCA)-induced 5-hydroxytryptamine (5-HT) depletions. Pretreatment of rats with the tyrosine hydroxylase inhibitor AMT before treatment with the serotonin neurotoxin pCA decreased the extent of 5-HT depletion in the two brain regions examined. In these experiments, rats were administered AMT (150 mg/kg) 1 and 5 hours prior to an injection of pCA (5, 10, or 15 mg/kg). AMT reduced the pCA-induced 5-HT depletions in the striatum and to a lesser extent in the hippocampus. Furthermore, the attenuation of neurotoxicity was dependent on dose of pCA, with greater AMT effects at higher doses of pCA. AMT-pretreated rats were still significantly depleted of brain 5-HT following all doses of pCA. However, at the higher doses of pCA, the AMT-pretreated rats were significantly less depleted than saline-pretreated, pCA-treated rats. These results suggest that the neurotoxic effects of high doses of pCA on 5-HT-containing nerve terminals may be in part dependent on the availability of newly synthesized dopamine (DA).