Higher long-lasting ethanol sensitization after adolescent ethanol exposure in mice

Abstract

Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is a possible consequence of ethanol exposure during adolescence. The aim of this study was to characterize the long-term alterations in the stimulant effects of ethanol and in the rate of ethanol sensitization in mice pre-exposed to ethanol during adolescence in comparison to mice pre-exposed to ethanol in adulthood. Adolescent and adult female Swiss mice were injected with saline or ethanol (2.5 or 4 g/kg) during 14 consecutive days. After a 3-week period of ethanol abstinence, mice were tested as adults before and after a second exposure to daily repeated ethanol injections. All mice pre-exposed to ethanol as adults or adolescents showed higher stimulant effects when re-exposed to ethanol 3 weeks later. However, this enhanced sensitivity to the stimulant effects of ethanol was of significantly higher magnitude in mice repeatedly injected with high ethanol doses (4 g/kg) during adolescence. Furthermore, the increased expression of ethanol stimulant effects in these mice was maintained even after a second procedure of ethanol sensitization. Adolescence is a critical period for the development of a sensitization to ethanol stimulant properties providing that high intermittent ethanol doses are administered. These results might contribute to explain the relationship between age at first alcohol use and risks of later alcohol problems and highlight the dangers of repeated consumption of high alcohol amounts in young adolescents.