Plasticity of GABAA receptors in brains of rats treated with chronic intermittent ethanol.
The study of alcohol dependence mechanisms has been aided by work in rodents, where regimens of intermittent chronic administration with repeated episodes of intoxication and withdrawal can be coupled with controlled timing of in vitro studies and the possibility of relating them to behavior. The chronic intermittent ethanol (CIE) model in the rat has been found to be a good model of human alcohol dependence, showing persistent signs of withdrawal and self-administration. Studies in CIE rats suggest that plastic changes in GABA-mediated inhibition involving the GABAA receptor system may be responsible for the behavioral alterations. Here we summarize a combination of evidence that the alcoholic rat CIE model demonstrates changes in GABAA receptor subunit levels, in receptor localization, and in physiology and pharmacology, leading to alterations in behavior that contribute to the hyperexcitable alcohol withdrawal state (anxiety, insomnia, seizure susceptibility) and alcohol dependence.
Olsen
Richard W
RW
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room CHS 23-120, 650 Young Drive South, Los Angeles, CA 90095-1735, USA. rolsen@mednet.ucla.edu
Liang
Jing
J
Cagetti
Elisabetta
E
Spigelman
Igor
I
D000818:Animals; D015536:Down-Regulation; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D023421:Models, Animal; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol