Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus.
Chronic exposure to stress levels of corticosteroids alters many aspects of hippocampal function and may lead to neurodegeneration. Male rats were treated for 10 days with corticosterone (CORT) or vehicle pellets, and mRNA levels for six gamma-aminobutyric acid (GABAA) receptor subunits were measured. Effects of castration on subunit mRNA levels in CORT- and vehicle-treated animals were also examined. In situ hybridization studies demonstrated that mRNA levels for hippocampal GABAA receptor alpha 1, alpha 2, beta 1, beta 2, beta 3, and gamma 2 subunits were differentially altered by CORT treatment. Levels of alpha 1 and alpha 2 mRNA decreased in the dentate gyrus, and beta 1 mRNA levels decreased in CA1 and dentate gyrus of CORT-, compared to vehicle-treated, animals. In contrast, beta 2 subunit levels increased in all hippocampal regions examined, beta 3 levels increased in the dentate gyrus, and gamma 2 levels increased in CA1-CA3. The alpha 1, beta 1, and beta 2 mRNA levels all increased in the cingulate cortex of CORT-treated animals. There was no significant effect of gonadal state on any of the subunits examined, but there was a significant negative correlation between testosterone levels and mRNA levels of alpha 1, alpha 2 and beta 3 in specific regions. These data demonstrate that chronic exposure to stress levels of CORT produces complex changes in the mRNA levels of multiple GABAA receptor subunits, independently of the CORT-induced suppression of circulating testosterone.
Orchinik
M
M
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.
Weiland
N G
NG
McEwen
B S
BS
D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003345:Corticosterone / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D013312:Stress, Physiological / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D013739:Testosterone; D003345:Corticosterone