On the mechanism of the acute decrease of rat brain tryptophan hydroxylase activity by 4-chloroamphetamine

The decrease of rat brain soluble tryptophan hydroxylase activity 4 h after the injection of 20 mg/kg i.p. of 4-chloroamphetamine was antagonized by 20 mg/kg i.p. of zimelidine, a selective inhibitor of membrane serotonin (5-HT) uptake, by 2.5 mg/kg i.p. of chlorpromazine and by 5 mg/kg i.p. of methergoline, a proposed antagonist of central 5-HT receptors, when these compounds were injected 15 min prior to 4-chloroamphetamine. Zimelidine partially reversed the fall in tryptophan hydroxylase when injected 4 h after 4-chloroamphetamine and the enzyme activity was recorded after further 4 h. Reserpine, 5 mg/kg i.p., 18 h before 4-chloroamphetamine prevented the decrease of the enzyme activity but had no effect when injected 1 h beforehand. It is suggested that the decrease of the tryptophan hydroxylase activity is secondary to the release of 5-HT and mediated by 5-HT receptor stimulation.