Cyclooxygenase inhibitors antagonize the rate-depressant effects of ethanol on fixed-ratio responding.

Prostaglandin synthetase inhibitors (PGSIs), which inhibit actions of the enzyme complex cyclooxygenase, significantly antagonize the effects of alcohols but not other sedative-hypnotics across a broad range of measures. This suggests that certain actions of alcohols, in particular ethanol, are mediated at least partially through a prostaglandin-related pathway. This study examined changes in the rate-depressant effects of ethanol in an operant task following pretreatment with either of two PGSIs, indomethacin (INDO) or aspirin (ASP). Water reinforcement maintained the responding of male Sprague-Dawley (SD) rats under a Fixed-Ratio (FR) 32 schedule. Saline, INDO or ASP had no significant effect on control rates of responding. INDO pretreatment significantly antagonized the rate-depressant effects of 1.0 and 1.5 g/kg ethanol. ASP pretreatment also resulted in significant antagonism of ethanol's rate-decreasing effects. INDO was more potent than ASP in antagonizing the rate-depressant effects of ethanol. These results provide further support for the hypothesis that alcohols, by fluidizing neuronal membranes and mobilizing the release of arachidonate, serve to increase prostaglandin production, resulting in some of the behavioral and physiological sequellae of ethanol administration.