Indomethacin antagonism of ethanol-induced sleep time: Sex and genotypic factors

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Abstract
Pretreatment with prostaglandin synthetase inhibitors (PGSI) significantly decreases the CNS effects of ethanol across the entire ethanol dose-response curve. PGSIs do not significantly affect ethanol metabolism. These effects have been shown in HS/Ibg, LS/Ibg, and SS/Ibg males and females. These strains of mice are useful in alcohol research but are not widely available. The present study examined the possibility of similar effects in C57BL/6 and C3H/2 mice of both sexes. PGSI pretreatment significantly reduced ethanol sleep time across both sexes and genotypes in a dose-dependent manner. Females of both strains required more PGSI to antagonize ethanol's actions relative to males. Within sex, mice with greater sensitivity to ethanol required more PGSI to optimally reduce sleep time than less sensitive mice. These results extend previous findings, and support out hypothesis that one of ethanol's primary mechanisms of action in the CNS is to increase the synthesis of prostaglandins.