ArticleNeuropharmacology2025
Adolescent intermittent ethanol exposure produces sex-specific development of functional tolerance to ethanol-induced motor impairment and hypothermia.
Article in Neuropharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Adolescent intermittent ethanol (AIE) exposure has been shown to attenuate sensitivity to ethanol effects, suggesting tolerance development. The present studies sought to determine whether AIE-exposed male and female rats would develop tolerance to ethanol-induced motor impairment and hypothermia, and to test the effects of AIE on ethanol-metabolizing enzymes in the brain. Adult rats showed motor impairment at 2 g/kg i.p. ethanol, with intoxicated practice attenuating ethanol-induced motor impairment (Experiments 1 & 2). AIE-exposed males, but not females, showed reduced motor impairment when challenged with 2 g/kg i.p. ethanol 1 day after AIE, suggesting tolerance development (Experiment 3). AIE-exposed males, but not females, became tolerant to ethanol-induced hypothermia during AIE (Experiment 4). Brain and/or blood ethanol levels were not affected by AIE. No tolerance was evident 30 days later. Gene expression of ethanol-metabolizing enzymes was assessed in animals with a history of AIE and challenged with 2.5 g/kg i.p. ethanol in adulthood (Experiment 5). In females, AIE reduced catalase (CAT) and aldehyde dehydrogenase 2 (ALDH2) expression in the amygdala. Males showed increased alcohol dehydrogenase 1 (ADH1) expression in the amygdala following an ethanol challenge. Experiment 6 revealed transient effects of AIE on cell-type-specific expression of ADH1 and ALDH2. One day after AIE, AIE-exposed males showed a reduction in ADH1 colocalized with neurons in the cerebellum, whereas AIE-exposed females showed a reduction in ALDH2, particularly in microglia, in the hippocampus. Together, these findings revealed sex-specific, short-term tolerance to ethanol-induced motor impairment and hypothermia during AIE that was independent of ethanol pharmacokinetics.
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