Early alcohol use is a major concern due to the dramatic rise in alcohol use during adolescence. In humans, adolescent males and females consume alcohol at equivalent rates; however, in adulthood males are more likely to consume harmful levels of alcohol. In animal models, the long-term dose-dependent and sex-dependent effects of alcohol exposure during adolescence have not been readily assessed relative to exposure that is initiated in adulthood. The purpose of the present set of experiments was to determine if adolescent exposure to chronic ethanol would predispose male and female rats to greater ethanol intake in adulthood when compared to animals that were not exposed to chronic ethanol exposure until early adulthood. Male and female rats were chronically administered 0.75 g/kg or 1.5 g/kg ethanol or saline for 21 days during adolescence (postnatal day (PND) 30–50) or adulthood (PND 60–80). All rats subsequently underwent 14-days of abstinence (PND 51–64 or PND 81–94, respectively). Finally, all rats were given 30-min daily access to saccharin-sweetened ethanol or saccharin alone from PND 65–80 for adolescent-exposed rats and PND 95–110 for adult-exposed rats. Exposure to 0.75 g/kg ethanol did not alter ethanol or saccharin intake in adolescent-exposed or adult-exposed rats, regardless of sex. In contrast, chronic exposure to the higher 1.5 g/kg dose during adolescence increased ethanol intake in adulthood in female rats. However, there was no change in saccharin intake in animals exposed to 1.5 g/kg ethanol during adolescence or adulthood, regardless of sex. Additionally, there were no clear age- and ethanol-dependent changes in duration of loss of righting reflex and blood ethanol concentrations to a challenge administration of a higher dose of ethanol. The results of the present set of experiments indicate chronic exposure to a high dose of ethanol during adolescence in female rats did indeed predispose rats to consume more ethanol in adulthood. Given that these effects were only observed in adolescent-exposed female rats, these results support a unique vulnerability to the long-term consequences of adolescent ethanol exposure in female rats, an effect that is not merely mediated by the sweetener used in the ethanol solution.
Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity
