Nicotine modulates evoked GABAergic transmission in the brain.
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 GABA(A) receptor antagonist, bicuculline (20 microM). Under voltage-clamp with KCl-filled pipettes (holding potential -70 mV), nicotine (0.1-1.0 microM) 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 microM) or diminished (0.5-1.0 microM) evoked GABAergic neurotransmission. Nicotine had no significant effect on the postsynaptic current induced by exogenous GABA (30-50 microM). 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.
Zhu
P J
PJ
Department of Pharmacology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
Chiappinelli
V A
VA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002642:Chick Embryo; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011963:Receptors, GABA-A / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013787:Thalamic Nuclei / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005731:Ganglionic Stimulants; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D005680:gamma-Aminobutyric Acid; D009538:Nicotine