Serotonin Agonists Reduce Dopamine Synthesis in the Striatum Only when the Impulse Flow of Nigro-Striatal Neurons Is Intact

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

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 γ-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-MeODMT 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 μg in 0.5 μl) 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.

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