title: Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.
abstract: Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent's unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however, age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this 4-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3+/-0.1g/kg/day) than adults (9.2+/-0.2g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5+/-10.2 and 338.5+/-7.8mg/dL, respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on withdrawal severity regardless of age.
authors.affiliation: Department of Pharmaceutical Sciences, The University of Kentucky, Lexington, 40536-0082, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Morris
authors.forename: M L
authors.initials: ML
authors.lastname: Kelso
authors.forename: D J
authors.initials: DJ
authors.lastname: Liput
authors.forename: S A
authors.initials: SA
authors.lastname: Marshall
authors.forename: K
authors.initials: K
authors.lastname: Nixon
mesh_terms: D000367:Age Factors; D000375:Aging; D019973:Alcohol-Related Disorders / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012720:Severity of Illness Index; D046468:Sexual Development; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol