Serotonin Inhibits Acetylcholine Release from Rat Striatum Slices: Evidence for a Presynaptic Receptor‐Mediated Effect

Abstract

Rat brain striatum slices were incubated with [³H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K⁺-enriched buffer for 2 min. The tritium overflow evoked by K⁺ was decreased by 5-hydroxytrytamine (serotonin, 5-HT) (maximal inhibition 10^–6M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyltryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K⁺-evoked overflow of tritium (³H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10^–6M) These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals.