Long-lasting facilitation of 4-amino-n-[2,3-H-3]butyric acid ([H-3]GABA) release from rat hippocampal slices by nicotinic receptor activation

In this study we explored the effect of the stimulation of nicotinic acetyl choline receptors located on interneurons by measuring 4-amino-n-[ 2,3-H-3] butyric acid ([H-3]GABA) release and monitoring [Ca2+](i) in superfused hi ppocampal slices. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione, (+/-)-2-amino- 5-phosphonopentanoic acid, and atropine, i.e., under the blo ckade of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate and mu scarinic receptors, nicotine did not alter the spontaneous outflow of [H-3] GABA, but significantly increased the stimulation-evoked [H-3] GABA efflux . This effect of nicotine depended on the time interval between nicotine tr eatment and electrical stimulus, the concentration of nicotine (1-100 muM), and the parameters of electrical depolarization. Acetylcholine (0.03-3 mM) , and the alpha7 subtype-selective agonist choline (0.1-10 mM), also potent iated stimulus-evoked release of [H-3] GABA, whereas 1,1-dimethyl-4-phenilp iperazinium iodide failed to increase the tritium outflow significantly. Th e effect of nicotine treatment was prevented by tetrodotoxin (1 muM) and by the nicotinic acetylcholine receptor antagonist mecamylamine (10 muM), and the alpha7 subtype-selective antagonists alpha -bungarotoxin (100 nM) and methyllycaconitine (10 nM), whereas dihidro-beta -erythroidine (20 nM) was without effect. Perfusion of 100 muM nicotine caused a [Ca2+](i) transient in about one-third of the tested interneurons; however, the response to sub sequent electrical stimulation remained unchanged. Inhibition of the GABA t ransporter system by nipecotic acid (1 mM) or by decreasing the bath temper ature to 12 degreesC abolished completely the effect of nicotine to potenti ate the stimulation-evoked release of GABA. These findings indicate that th e activation of alpha7-type nicotinic receptors of hippocampal interneurons results in a long-lasting ability of these cells to respond to depolarizat ion with an increased release of GABA mediated by the transporter system.