CIRCADIAN-RHYTHMS IN THE BIOLOGICAL RESPONSE AND DISPOSITION OF ETHANOL IN THE MOUSE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (1) , 1-8
Abstract
Circadian rhythms in the response to ethanol [ET] were investigated in male, Swiss-Webster mice. Significant circadian variations were observed in increased and decreased spontaneous locomotor activity induced by ET (2 or 4 mg/g i.p., respectively) and in the hypothermic response to ET with the greatest effect generally occurring during the dark phase of the 12 h:12 h. light-dark cycle when the normal activity of the animals was highest. ET was also more lethal during the dark phase as compared to the light phase. Disposition studies showed that the in vivo rate of disappearance of ET from the blood and the in vitro metabolism of ET by hepatic alcohol dehydrogenase were invariant throughout the 24 h period. Additional studies demonstrated that the duration of ET-induced hypnosis was longer and the concentration of ET in blood and brain tissue, at awakening, was lower during the dark phase as compared to the light phase. Circadian rhythms observed in the pharmacological and toxicological effects of ethanol in mice apparently do not result from daily fluctuations in drug disposition but are more likely subserved by temporal changes in the sensitivity of the CNS to ET.