Serotonergic Modulation of Acetylcholine Release from Cortex of Freely Moving Rats1

The modulation of acetylcholine (ACh) release by 5-HT3 recep-tor activation was studied using in vivo microdialysis. Sponta-neous and K1-stimulated ACh release were measured in fron-toparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K1 produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-depen-dent decrease of K1-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 ago-nists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K1-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-a