Abstract
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.
Footnotes
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Send reprint requests to: Dr. Patrizio Blandina, Dip. di Farmacologia Preclinica e Clinica, Universitá di Firenze, V.le G.B. Morgagni 65, 50134 Firenze, Italy.
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↵1 This work was supported by Grant 60% from M.U.R.S.T- Universitá di Firenze (Italy).
- Abbreviations:
- ACh
- acetylcholine
- m-Cl-PBG
- m-chlorophenylbiguanide
- HPLC
- high-performance liquid chromatography
- 5-HT
- serotonin
- 8-OH-DPAT
- 8-hydroxy-2-(di-n-propylamino)tetralin
- Tropisetron (ICS 205–930)
- (3α-tropanyl)1H-indole-3-carboxylic acid ester
- PBG
- 1-phenylbiguanide
- ANOVA
- analysis of variance.
- Received July 7, 1997.
- Accepted February 16, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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