Further Studies on the Neurochemical Mechanisms Mediating Differences in Ethanol Sensitivity in LS and SS Mice

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Abstract
Long-sleep (LS) and short-sleep (SS) lines of mice were selectively bred for differences in CNS sensitivity to ethanol with LS mice exhibiting much greater sensitivity to hypnotic doses of ethanol (4.0-4.5 g/kg) than SS mice. The influence of peripheral and central catecholamine neuronal systems on ethanol sensitivity (sleep time) in LS and SS mice was examined following administration of reserpine, .alpha.-methyl-p-tyrosine and 6-hydroxydopamine. Ten days after a single dose of reserpine, tyrosine hydroxylase activity was increased in the brain and adrenal gland of LS mice but only in the brain of SS mice relative to untreated mice. Brain catecholamine levels in the reserpine-treated mice were 25-50% lower in both LS and SS mice compared to levels in untreated mice. These changes were associated with a 41% reduction in LS sleep time, but a 90% increase in SS sleep time. SS mice were also more susceptible to the lethal effects of reserpine. The increased mortality of SS mice may relate to a greater degree of reserpine-induced hypothermia and a slower rate of recovery of brain catecholamine levels. Neonatal LS and SS mice treated with 6-hydroxydopamine exhibited increased levels of catecholamines in the locus cereleus, decreased levels in the cerebellum and unchanged levels in the hypothalamus at 60 days of age. These changes were associated with a modest decrease (10%) in LS sleep time and a marked increase (200%) in SS sleep time. .alpha.-Methyl-p-tyrosine decreased brain catecholamine levels of both lines by 30-50% while LS sleep times were unchanged and SS sleep times were increased by 45%. These contrasting alterations in ethanol sensitivity in LS and SS mice follwing alterations in the levels of tyrosine hydroxylase activity or catecholamines suggest that catecholamine neuronal systems are involved in the differential response to ethanol. The results further suggest that catecholamine systems may be important in antagonizing the depressant effects of ethanol in SS mice, whereas catecholamine systems in LS mice may not be activated to a significant degree to neutralize the depressant actions of ethanol.