TY - JOUR T1 - Serotonergic Modulation of Acetylcholine Release from Cortex of Freely Moving Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1219 LP - 1225 VL - 285 IS - 3 AU - Maria Grazia Giovannini AU - Ilaria Ceccarelli AU - Beatrice Molinari AU - Marco Cecchi AU - Joseph Goldfarb AU - Patrizio Blandina Y1 - 1998/06/01 UR - http://jpet.aspetjournals.org/content/285/3/1219.abstract N2 - The modulation of acetylcholine (ACh) release by 5-HT3receptor activation was studied using in vivomicrodialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1Aagonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3antagonist, tropisetron ((3-α-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors. The American Society for Pharmacology and Experimental Therapeutics ER -