Serotonergic modulation of acetylcholine release from cortex of freely moving rats

Maria Grazia Giovannini, Ilaria Ceccarelli, Beatrice Molinari, Marco Cecchi, Joseph Goldfarb, Patrizio Blandina

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The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. 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-HT(1A) agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, 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.

Original languageEnglish
Pages (from-to)1219-1225
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - Jun 1998


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