Circadian rhythms in the biological response and disposition of ethanol in the mouse

Circadian rhythms in the response to ethanol were investigated in male, Swiss-Webster mice. Significant circadian variations were observed in increased and decreased spontaneous locomotor activity induced by ethanol (2 or 4 mg/g i.p., respectively) and in the hypothermic response to ethanol with the greatest effect generally occurring during the dark phase of the 12 hr:12 hr. light-dark cycle when the normal activity of the animals was highest. Ethanol was also more lethal during the dark phases as compared to the light phase. Disposition studies showed that the in vivo rate of disappearance of ethanol from the blood and the in vitro metabolism of ethanol by hepatic alcohol dehydrogenase were invariant throughout the 24-hr period. Additional studies demonstrated that the duration of ethanol-induced hypnosis was longer and the concentration of ethanol in blood and brain tissue, at awakening, was lower during the dark phase as compared to the light phase. These data suggest that circadian rhythms observed in the pharmacological and toxicological effects of ethanol in mice do not result from daily fluctuations in drug disposition but are more likely subserved by temporal changes in the sensitivity of the central nervous system to ethanol.