Behavioral and metabolic interaction between gossypol and ethanol.

The effects of gossypol on ethanol-elicited responses pertaining to liver ethanol, acetaldehyde-metabolizing enzymes and alcohol preference were studied in rodents. Intraperitoneal injection of a single dose of gossypol, 100 mg/kg, inhibited hepatic alcohol dehydrogenase for 50 h in mice from both sexes. The acute gossypol treatment produced earlier inhibition of mouse liver cytoplasmic aldehyde dehydrogenase in male than female mice. Acute gossypol administration initially inhibited mouse liver subcellular mitochondrial aldehyde dehydrogenase in both sexes which was not evident 50 h later. Administration of gossypol, 10 mg/kg i.p., to male rats with preference for ethanol caused aversion for ethanol drinking. The enzymatic determinations indicate gender sensitivity of subcellular mouse liver aldehyde dehydrogenase to gossypol. The behavioral study suggests adverse metabolic interaction between gossypol and alcohol which may underlie the rat aversion to voluntary ethanol drinking.