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Journal of Pharmacology and Experimental Therapeutics

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OtherBEHAVIORAL PHARMACOLOGY

Serotonergic Modulation of Acetylcholine Release from Cortex of Freely Moving Rats

Maria Grazia Giovannini, Ilaria Ceccarelli, Beatrice Molinari, Marco Cecchi, Joseph Goldfarb and Patrizio Blandina
Journal of Pharmacology and Experimental Therapeutics June 1998, 285 (3) 1219-1225;
Maria Grazia Giovannini
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Ilaria Ceccarelli
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Beatrice Molinari
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Marco Cecchi
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Joseph Goldfarb
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Patrizio Blandina
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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

  • 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.

  • ↵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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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 3
1 Jun 1998
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OtherBEHAVIORAL PHARMACOLOGY

Serotonergic Modulation of Acetylcholine Release from Cortex of Freely Moving Rats

Maria Grazia Giovannini, Ilaria Ceccarelli, Beatrice Molinari, Marco Cecchi, Joseph Goldfarb and Patrizio Blandina
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1219-1225;

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OtherBEHAVIORAL PHARMACOLOGY

Serotonergic Modulation of Acetylcholine Release from Cortex of Freely Moving Rats

Maria Grazia Giovannini, Ilaria Ceccarelli, Beatrice Molinari, Marco Cecchi, Joseph Goldfarb and Patrizio Blandina
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1219-1225;
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