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Modification of environmentally cued tolerance to ethanol in mice.

Tolerance to the hypnotic and hypothermic effects of ethanol in mice develops with multiple injections. The tolerance to both of these effects of ethanol can be reduced by testing the animals in a novel environment, suggesting that the tolerance may be learned. Tolerance to the hypothermic effect of ethanol develops more rapidly than tolerance to the hypnotic effect. Disruption of the brain catecholamine systems, with either 6-hydroxydopamine or alpha-methyl-p-tyrosine slows the rate of development of tolerance to the hypnotic effect of ethanol. Intraventricular injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine, increases initial sensitivity to ethanol-induced narcosis and facilitates the development of tolerance to the hypnotic effects of ethanol. Tolerance to the hypothermic effect of ethanol in a familiar environment is unaffected by either of the neurotoxins or by alpha-methyl-p-tyrosine. However, initial sensitivity to the temperature-lowering effect of ethanol is increased by 6-hydroxydopamine and decreased by alpha-methyl-p-tyrosine administration. Learning may be an important factor in development of tolerance to ethanol under some conditions and tolerance produced under these conditions can be modified by disruption of central catecholamine systems.