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).
Axt
K J
KJ
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Seiden
L S
LS
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D008781:Methyltyrosines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D019805:alpha-Methyltyrosine; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D008781:Methyltyrosines; D012701:Serotonin; D010133:p-Chloroamphetamine; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase