Evidence of the modulatory role of serotonin in acetylcholine release from striatal interneurons.

The release of acetylcholine was studied in isolated striatal slices of the rat. The spontaneous and ouabain-stimulated release of acetylcholine was higher in those slices where serotonergic input was somehow impaired: raphe nuclei lesion or p-chlorophenylalanine pretreatment or 5, 7-dihydroxytryptamine pretreatment resulted in a higher release. L-(m-chlorophenyl)-piperazine, a pure serotonin receptor stimulant and D-fenfluramine, a serotonin releaser significantly reduced the release of acetylcholine evoked by ouabain. Serotonin antagonists (cyproheptadine, mianserine and methysergide) prevented the effect of serotonin agonists. When the serotonergic neurons were destroyed either by p-chlorophenylalanine or by 5, 7-dihydroxytryptamine pretreatment D-fenfluramine had no inhibitory action; however, the effect of L-(m-chlorophenyl)-piperazine was not affected. It is suggested that there is a link between serotonergic and cholinergic neurons in the striatum: serotonin released from raphe-striatal neurons is able to inhibit the release of acetylcholine from striatal interneurons.