Withdrawal from Brief Repeated Alcohol Treatment in Adolescent and Adult Male and Female Rats.

Background: Early initiation of alcohol drinking has been associated with increased risk of alcohol dependence in adulthood. Although negative affect mediated in part by corticotropin-releasing factor (CRF) is a strong motivator for alcohol consumption in adults, comparisons of alcohol withdrawal in adolescents and adults generally have not included CRF-related measures such as anxiety. The purpose of the present study was to compare withdrawal signs including anxiety-like behavior after a brief multiday alcohol treatment in adolescent and adult male and female rats.

Methods: Animals were treated with a 5-day regimen of alcohol injections (3 daily intraperitoneal injections of 1.5 g/kg at 3-hour intervals, total of 15) starting on postnatal day (PN) 28 or PN 70. Spontaneous withdrawal signs and anxiety-like behavior (light/dark box) were assessed 18 hours after the last injection as described. One cohort of rats was treated with alcohol, killed 18 hours after the last injection, and blood was collected to assess corticosterone. Another cohort of rats was treated with alcohol or vehicle, given 1, 2, or 3 alcohol injections (1.5 g/kg), and killed 1 hour after final injection to determine blood alcohol concentration (BAC). Finally, adult and adolescent males and females received 5 days of alcohol or vehicle treatment followed by a final challenge with alcohol (3 g/kg), and blood was collected for corticosterone.

Results: BAC was comparable in adolescents and adults. Spontaneous withdrawal signs were comparable in adolescents and adults, and no sex differences were observed. Anxiety-like behaviors (time and distance in light, latency to emerge, and light entries) differed in alcohol- and vehicle-treated adults but not adolescents. Corticosterone was not elevated at withdrawal. Alcohol increased corticosterone significantly in vehicle-treated animals, but both adolescents and adults were tolerant to alcohol-induced elevation of corticosterone after 5 days of alcohol treatment.

Conclusions: These findings suggest that adolescents experience milder negative affect during withdrawal from brief alcohol exposures relative to adults but comparable suppression of hypothalamic-pituitary-adrenal axis function.