Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus.
Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAA receptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (1-12 weeks) ethanol treatment paradigm was used to evaluate changes in GABAA receptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of alpha 1 and alpha 5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration, cortical and cerebellar alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA, levels of alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, alpha 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAA receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol.
Charlton
M E
ME
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, New Haven 06508, USA.
Sweetnam
P M
PM
Fitzgerald
L W
LW
Terwilliger
R Z
RZ
Nestler
E J
EJ
Duman
R S
RS
D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D018079:Receptors, GABA; D000431:Ethanol