Effects of p-chlorophenylalanine and alpha-methyltryptophan on behaviour and brain 5-hydroxyindoles.

Abstract

The effects on rats of two drugs that reduce brain 5-hydroxytryptamine synthesis by different mechanisms were compared. Locomotor activity and home cage behaviour during the dark period, food intake and brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid concentrations were measured. p -Chlorophenylalanine (100 and 200 mg/kg), which decreases brain 5-hydroxytryptamine by inhibiting tryptophan hydroxylase, increased locomotion and social behaviour but reduced selfgrooming. α-Methyltryptophan (150 mg/kg), which decreases brain 5-hydroxytryptamine synthesis by lowering brain tryptophan through the induction of tryptophan pyrrolase, did not significantly alter locomotion or social behaviour but increased self-grooming and burrowing. Both drugs appeared to reduce 5-hydroxytryptamine turnover since they decreased brain 5-hydroxyindoleacetic acid concentrations. When tryptophan hydroxylase was inhibited by pretreatment with p -chlorophenylalanine. sub- sequent administration of α-methyltryptophan did not significantly alter the behavioural effects of p -chlorophenylalanine. These results are consistent with the behavioural effects of α-methyltryptophan being due to α-methyl-5-hydroxytryptamine which is synthesized from it by the action of tryptophan hydroxylase. α-Methyl-5-hydroxytryptamine was determined as apparent 5-hydroxytryptamine and is suggested to oppose the behavioural effects of the decreased 5-hydroxytryptamine synthesis. α-Methyltryptamine, a minor metabolite of α-methyltryptophan, caused marked hyperactivity without social behaviour, self-grooming or burrowing, and thus appears not to be involved in the behavioural results of α-methyltryptophan administration.