Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice

Abstract

The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8–10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12–16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared. The coemergence during development of differences between LS and SS mice in behavioral (sleep time and hypothermia) and neurochemical (depression of monoamine synthetic activity) sensitivity to ethanol are consistent with the hypothesis that differences in the response of monoamine systems to ethanol in LS and SS contribute to their differential CNS ethanol sensitivity.