Inhibition of 5-hydroxytryptamine uptake by tetrahydronorharmane in vivo.

Injection of tetrahydronorharmane (THN) elicited a dose-dependent increase of the level of 5-hydroxytryptamine (5-HT) and a fall of 5-hydroxyindoleacetic acid in the rat brain whereas noradrenaline and dopamine levels remained unchanged. The effect on indoles was shortlasting which may be explained by the short half life of THN or its metabolization to 6-OH-THN. The 5-HT depleting action of parachloro-N-methylamphetamine (CMA) was used to study uptake inhibition in vivo. The results support the notion that THN acts as an inhibitor of the reuptake of 5-HT in vivo. Further evidence for this hypothesis was obtained by intraventricular injection of radiolabelled 5-HT. The disappearance of (3H)-5-HT from brain tissue was reduced by THN. Thus, THN may exert its central 5-HT-like effects in pharmacological experiments by preventing 5-HT from being removed from the synaptic cleft.