The aim of this study was to investigate the role of the 5-HT receptors in acetylcholine (ACh) release from the striatum. Slices from the rat striatum and synaptosomes were incubated with [sup>3H]-choline and the release of the labelled
products
was evoked by electrical (3 ㎐, 2 ㎳, 5 V/㎝, rectangular pulses, 2 min) and potassium-stimulation (25 mM), respectively, and the influence of various serotonergic drugs on the evoked tritium outflows was investigated. Serotonin decreased the
electrically-evoked ACh release in striatum in a concentration-dependent manner without the change of basal release. In hippocampal and entorhinal cortical slices, serotonin did not affect the evoked and basal release of ACh, but, at large dose
(30
μM)
decreased the evoked ACh release in hippocampus. 2,5-Dimethoxy-4-iodoamphetamine (DOI), a specific 5-HT2A/2C agonist, decreased evoked ACh release in the striatum. CGS-12066A (5-HT 1B agonist), m-chlorophenyl-biguanide
(5-HT3 agonist) and 5-[(dimethyl -amino)methyl]-3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazole (5-HT3 antagonist) did not affect the evoked and basal ACh release in all tissues. Ritanserin, a specific 5-HT2A/2C
antagonist,
blocked the inhibitory effects of serotonin and DOI, whereas, ketanserin, an another type of specific 5-HT2A/2C antagonist did not affect the inhibitory effects of serotonin and DOI. In striatal synaptosomal preparation, serotonin and
DOI did
not affect the K+-evoked ACh release. These findings suggest that ritanserin-sensitive 5-HT2A/2C receptors located in the soma and/or axons of the striatal cholinergic neurons play a important role in ACh release.
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