Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.

In rats, two serotonin agonists, 5-MeO-DMT and CPP, did not reduce dopamine synthesis in the striatum when impulse flow in dopamine neurons was blocked by gamma-butyrolactone, unlike the dopamine agonist apomorphine. However, when impulse flow was intact, both serotonin agonists did reduce dopamine synthesis. Injecting serotonin directly into the substantia nigra increased dopamine synthesis, similar to blocking impulse flow. The findings suggest that serotonin agonists affect dopamine synthesis indirectly, possibly through other neurons like cholinergic or GABA-ergic ones, and only when dopamine neurons are active.

Study at a glance

Abstract

The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.