Nicotine Modulates Evoked GABAergic Transmission in the Brain

Abstract

The effects of nicotine on evoked GABAergic synaptic transmission were examined using whole cell recordings from neurons of the lateral spiriform nucleus in embryonic chick brain slices. All synaptic activities were abolished by the GABAA receptor antagonist, bicuculline (20 μM). Under voltage-clamp with KCl-filled pipettes (holding potential −70 mV), nicotine (0.1–1.0 μM) increased the frequency of spontaneous GABAergic currents in a dose-dependent manner. Nicotine enhanced electrically evoked GABAergic transmission only at relatively low concentrations of 50–100 nM (but not 25 nM), which approximate the concentrations of nicotine in the blood produced by cigarette smoking. At higher concentrations nicotine had either no effect (0.25 μM) or diminished (0.5–1.0 μM) evoked GABAergic neurotransmission. Nicotine had no significant effect on the postsynaptic current induced by exogenous GABA (30–50 μM). These data imply that nicotine levels attained in smokers are sufficient to enhance evoked GABAergic transmission in the brain, and that this effect is most likely mediated through activation of presynaptic nicotinic receptors.