Reduction of tryptophan hydroxylase activity and 5-hydroxytryptamine concentration in certain rat brain nuclei after p-chloroamphetamine.

High-pressure liquid chromatography and mass fragmentography have been used to determine tryptophan hydroxylase activity and 5-hydroxytryptamine (5-HT) concentration, respectively, in certain rat brain nuclei. (+/-)-p-Chloroamphetamine (100 mumol/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 months 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 the 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. These results suggest that the primary site of action of p-chloroamphetamine is on nerve terminals followed by secondary effects on serotonergic cell bodies.