Role of the GABA-A system in estrogen-induced protection against brain lipid peroxidation in ethanol-withdrawn rats.
BACKGROUND
Our previous study showed that 17 beta-estradiol (E2) treatment protects against cerebellar neuronal death and related motor deficits in ethanol-withdrawn rats, in part through the GABAergic system. In this study, we examined the effect of the GABA-A antagonist bicuculline on the neuroprotective effect of E2 by assessing the oxidative marker thiobarbituric acid reactive substances (TBARS) during ethanol withdrawal (EW).


METHODS
Ovariectomized animals that had implants of E2 (EW/E2) or oil (EW/Oil) pellets received liquid ethanol (7.5% w/v) or dextrin for 7 days by gavage. The GABA-A antagonist bicuculline (1.25 mg/kg) was administered (three times a day intraperitoneally) for 4 days starting 3 days before the onset of EW. After testing for overt EW signs at 7 hr of EW, one set of the animals was immediately killed for the collection of the cerebellum, hippocampus, and cortex. The brain homogenates were further processed for TBARS assay to detect TBARS in the presence or absence of FeCl(3). For assessing motor capacity, the other set of animals was tested for the latency to fall from a rotarod after 1 week of EW.


RESULTS
The EW/Oil animals had enhanced endogenous and FeCl(3)-stimulated TBARS levels in the cerebellum and the hippocampus in a manner potentiated by bicuculline but inhibited by E2. Bicuculline counteracted the protective effect of E2 when administered along with E2. Pearson correlation coefficients indicated that the latency to fall from the rotarod covaried with TBARS levels in the cerebellum and the hippocampus.


CONCLUSIONS
These data suggest that E2 protects against lipid peroxidation in vulnerable brain areas of ethanol-withdrawn rats, in part through the GABAergic system.
Rewal
Mridula
M
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA. mrewal@hsc.unt.edu
Jung
Marianna E
ME
Simpkins
James W
JW
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D004967:Estrogens; D011963:Receptors, GABA-A; D000431:Ethanol