Regional differences in the response of serotonergic neurons in rat CNS to drugs

In vivo rates of 5-hydroxytryptophan accumulation (following administration of the decarboxylase inhibitor R04/4602/1) and levels of 5-HT in the nucleus raphe dorsalis (DR), nucleus centralis superior (NCS), nucleus septalis lateralis (LS), nucleus suprachiasmaticus (SCN), nucleus hypothalamicus anterior (AH), and nucleus amygdaloideus centralis (AG) were determined following administration of fluoxetine, 5-methoxy-N,N-dimethyltryptamine, methiothepin, L-tryptophan and reserpine. Fluoxetine and 5-methoxy-N,N-dimethyltryptamine inhibited 5-hydroxytryptophan synthesis in all nuclei, although inhibition of synthesis in the DR was resistant to fluoxetine. Methiothepin inhibited 5-HT synthesis in the DR, NCS, LS and AG, but not in the SCN or AH. L-Tryptophan greatly increased 5HT synthesis in all areas, but this increase was not uniform, being fourfold greater in the NCS than in the LS. Reserpine, while greatly depleting 5HT did not increase 5-hydroxytryptophan synthesis in any nucleus. In no region could changes in brain tryptophan account for the observed drug effects on serotonin metabolism. We conclude that not all CNS serotonergic structures respond to the same drug in a uniform manner.