INHIBITORY ROLE FOR BRAIN SEROTONIN-CONTAINING SYSTEMS IN LOCOMOTOR EFFECTS OF D-AMPHETAMINE

Abstract

Locomotor activity induced by d-amphetamine was potentiated by food deprivation, a tryptophan-free diet, p-chlorophenylalanine and drugs proposed to antagonize serotonin receptors in brain. Administration of L-tryptophan 1 h prior to d-amphetamine injection antagonized the enhanced response to d-amphetamine in starved rats and in rats which had tryptophan removed from their diet. Tryptophan did not block the potentiated response to d-amphetamine in animals pretreated with p-chlorophenylalanine. The antagonism of d-amphetamine-induced activity by tryptophan in starved rats and rats fed a tryptophan-free diet was not due to a nonspecific depressant effect of the amino acid. Since accumulation of d-amphetamine and its metabolites was not affected by any of the treatments which enhanced its activity, it seems unlikely that an alteration in the metabolism of d-amphetamine can explain these findings. Additional support for the view that serotonergic fibers play an important role in the actions of d-amphetamine was provided.