title: Evidence for modulation of GABAergic neurotransmission by nicotine.
abstract: Bath-application of nicotine (800 microM) to mouse hippocampal slices resulted in an increase in the amplitude of the population spike and the appearance of multiple population spikes in the CA1 pyramidal cell layer. Similar effects were observed after perfusion of the GABAA antagonist bicuculline methiodide (2 microM) and the glutamate decarboxylase inhibitor L-C-allylglycine (4 mM). These apparently excitatory effects of nicotine (800 microM) could be reversed by bath-application of gamma-aminobutyric acid (GABA; 400 microM), as well as by the GABA uptake inhibitor nipecotic acid (5 mM) and the benzodiazepine flurazepam (4 microM). Nicotine did not alter binding of [3H]GABA or [3H]flunitrazepam to whole brain plasma membranes. The results are consistent with the hypothesis that the electrophysiological effects of nicotine on CA1 pyramidal cell excitability is mediated by disruption of GABAergic transmission.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
authors.forename: R K
authors.initials: RK
authors.lastname: Freund
authors.forename: D A
authors.initials: DA
authors.lastname: Jungschaffer
authors.forename: A C
authors.initials: AC
authors.lastname: Collins
authors.forename: J M
authors.initials: JM
authors.lastname: Wehner
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D000501:Allylglycine; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D009538:Nicotine; D005968:Glutamate Decarboxylase; D001640:Bicuculline