REDUCTION OF TRYPTOPHAN-HYDROXYLASE ACTIVITY AND 5-HYDROXYTRYPTAMINE CONCENTRATION IN CERTAIN RAT-BRAIN NUCLEI AFTER PARA-CHLOROAMPHETAMINE

Abstract

High-pressure liquid chromatography and mass fragmentography were used to determine tryptophan hydroxylase activity and 5-hydroxytryptamine (5-HT) concentration, respectively, in certain rat brain nuclei. (.+-.)-p-Chloroamphetamine (100 .mu.mol/kg i.p.) decreased enzyme activity in 5-HT terminals of the caudate, hippocampus and septum to a minimum level within 3 days. In hippocampus but not in septum, the enzyme activity and 5-HT content remained maximally depleted (about 80%) for as long as 2 mo. after the p-chloroamphetamine injection. Of the 5-HT cell body areas investigated, only in the B9 nucleus was the tryptophan hydroxylase activity and 5-HT content still significantly reduced (about 25-50%) at 21 and 60 days after drug injection. The enzyme activity and 5-HT content of the B7 and B8 nuclei were not significantly different from control values at these times. Possibly the primary site of action of p-chloroamphetamine is on nerve terminals followed by secondary effects on serotonergic cell bodies.