Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.
Journal of neurochemistry – September 01, 1985
Source: PubMed
Summary
5-MeO-DMT and CPP did not significantly lower the increase of DOPA in the striatum of rats treated with gamma-butyrolactone (GBL), unlike apomorphine, which effectively reduced DOPA levels at 2 mg/kg. In contrast, both substances decreased DOPA accumulation when combined with a decarboxylase inhibitor. Additionally, serotonin injections boosted DOPA levels similarly to GBL. These findings suggest that serotonin agonists influence dopamine synthesis in the striatum primarily when dopamine neuron activity is intact, hinting at complex regulatory mechanisms involving other neurotransmitters.
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.