Nicotinic Agonist Modulation of Neurotransmitter Levels in the Rat Frontoparietal Cortex.

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  • Summers Kathleen L.
    Department of Pharmacology, Southern Illinois University
  • Kem William R.
    Department of Pharmacology and Therapeutics, College of Medicine, University of Florida
  • Giacobini Ezio
    Department of Pharmacology, Southern Illinois University Dept. of Geriatrics, University of Geneva, Medical School

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  • Nicotinic Agonist Modulation of Neurotr

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Anabaseine is a naturally occurring toxin that stimulates a variety of neuronal and muscle nicotinic receptors. GTS-21 [3-(2, 4-dimethoxybenzylidene)anabaseine], an anabaseine derivative, selectively stimulates α7-containing nicotinic receptors. Here we report the first in vivo study of the effects of these two nicotinic agonists on cortical extracellular acetylcholine (ACh), dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels, measured with a microdialysis probe placed within the frontoparietal cortex in the absence of a cholinesterase inhibitor. At 3.6 μmol/kg, s.c., anabaseine increased cortical ACh and NE above baseline values without significantly affecting DA and 5-HT. The ACh and NE elevations were inhibited by i.p. pre-administration (4.9 μmol/kg) of the nicotinic antagonist mecamylamine (Mec). In contrast, GTS-21 (3.6 μmol/kg, s.c.)significantly increased NE and DA without affecting ACh and 5-HT levels. Following Mec injection, GTS-21 increased ACh 25-fold and 5-HT 13-fold, while NE and DA levels were slightly decreased in comparison with GTS-21 alone. We suggest that at the dose used, Mec may preferentially block high affinity nicotinic receptors which normally provide an inhibitory influence upon ACh release, thereby permitting expression of the complete stimulatory effect of GTS-21 on neuronal α7-receptors. GTS-21 and other receptor subtype-selective nicotinic agonists should be helpful in clarifying the roles of particular nicotinic receptors in modulating cortical neurotransmitter levels.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 74 (2), 139-146, 1997

    公益社団法人 日本薬理学会

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