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Vol. 295, Issue 2, 453-462, November 2000

Long-Lasting Facilitation of 4-Amino-n-[2,3-3H]butyric Acid ([3H]GABA) Release from Rat Hippocampal Slices by Nicotinic Receptor Activation1

Attila Köfalvi, Beáta Sperlágh, Tibor Zelles and E. Sylvester Vizi

Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

In this study we explored the effect of the stimulation of nicotinic acetylcholine receptors located on interneurons by measuring 4-amino-n-[2,3-3H]butyric acid ([3H]GABA) release and monitoring [Ca 2+]i in superfused hippocampal slices. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione, (±)-2-amino-5-phosphonopentanoic acid, and atropine, i.e., under the blockade of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate and muscarinic receptors, nicotine did not alter the spontaneous outflow of [3H]GABA, but significantly increased the stimulation-evoked [3H]GABA efflux. This effect of nicotine depended on the time interval between nicotine treatment and electrical stimulus, the concentration of nicotine (1-100 µM), and the parameters of electrical depolarization. Acetylcholine (0.03-3 mM), and the alpha 7 subtype-selective agonist choline (0.1-10 mM), also potentiated stimulus-evoked release of [3H]GABA, whereas 1,1-dimethyl-4-phenilpiperazinium iodide failed to increase the tritium outflow significantly. The effect of nicotine treatment was prevented by tetrodotoxin (1 µM) and by the nicotinic acetylcholine receptor antagonist mecamylamine (10 µM), and the alpha 7 subtype-selective antagonists alpha -bungarotoxin (100 nM) and methyllycaconitine (10 nM), whereas dihidro-beta -erythroidine (20 nM) was without effect. Perfusion of 100 µM nicotine caused a [Ca2+]i transient in about one-third of the tested interneurons; however, the response to subsequent electrical stimulation remained unchanged. Inhibition of the GABA transporter system by nipecotic acid (1 mM) or by decreasing the bath temperature to 12°C abolished completely the effect of nicotine to potentiate the stimulation-evoked release of GABA. These findings indicate that the activation of alpha 7-type nicotinic receptors of hippocampal interneurons results in a long-lasting ability of these cells to respond to depolarization with an increased release of GABA mediated by the transporter system.


1 This work was supported by a Philip Morris research grant and by the grants of Hungarian Research Foundation (OTKA), and the Hungarian Medical Research Council (ETT). Some information contained in this article was presented in preliminary form at the 29th Annual Meeting of Society for Neuroscience in Miami Beach, Florida (Sperlágh et al., 1999).


0022-3565/00/2952-0453$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics



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