title: Effects of chronic ethanol consumption on rat GABA(A) and strychnine-sensitive glycine receptors expressed by lateral/basolateral amygdala neurons.
abstract: It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.
authors.affiliation: Department of Medical Pharmacology and Toxicology, Texas A&M System H.S.C., College Station, TX 77843, USA. bmccool@wfubmc.edu
authors.forename: Brian A
authors.initials: BA
authors.lastname: McCool
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Frye
authors.forename: Marisa D
authors.initials: MD
authors.lastname: Pulido
authors.forename: Shaleen K
authors.initials: SK
authors.lastname: Botting
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000378:metabolism / Q000523:psychology; D001569:Benzodiazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018009:Receptors, Glycine / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D018684:Glycine Agents; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D001569:Benzodiazepines; D000431:Ethanol; D013331:Strychnine; D008874:Midazolam