Ontogeny of the stimulant and sedative effects of ethanol in male and female Swiss mice: gradual changes from weaning to adulthood

Abstract

Rationale: The adolescent period is characterized by a specific sensitivity to the effects of alcohol, which is believed to contribute to the enhanced risks of alcohol dependence when drinking is initiated early during adolescence. In adolescent rodents, while the reduced sensitivity to the sedative effects of ethanol has been well characterized, its stimulant effects have not yet been extensively studied.

Objectives: The present study characterized the development of the stimulant and the sedative effects of acute ethanol in male and female Swiss mice from weaning to early adulthood and tested whether both effects are interrelated.

Methods: In a first experiment, mice aged 21, 28, 35, 42, and 60 days were injected with various ethanol doses and tested for ethanol-induced locomotor activity. In an independent experiment, mice of the same groups of age were injected with 4 g/kg ethanol and ethanol-induced sedation was quantified with the loss of righting reflex procedure.

Results: In male and female mice, the stimulant effects of ethanol gradually decreased, whereas its sedative effects increased with age. When the sedation was statistically controlled using a covariance analysis, the differences between adult and juvenile mice in the locomotor stimulation were significantly reduced.

Conclusions: From weaning to early adulthood, the acute stimulant and sedative effects of ethanol show gradual changes that are similar in male and female mice. Although the initial tolerance to the sedative effects of ethanol contributes to the changes in ethanol-induced locomotor activity, young mice also show a higher sensitivity to the stimulant effects of ethanol.