Long-term ethanol self-administration induces Delta-Fos B in male and female adolescent, but not in adult, Wistar rats

WILLE-BILLE, ARANZA; DE OLMOS, S; MARENGO, L; CHINER, F.; PAUTASSI R.M.

PROGRESS OF NEUROPSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2017 vol. 74 p. 15 - 30

0278-5846

Early-onset ethanol consumption predicts later development of alcohol use disorders. Age-related differences inreactivity to ethanol's effects may underlie this effect. Adolescent rats are more sensitive and less sensitive thanadults to the appetitive and aversive behavioral effects of ethanol, respectively, and more sensitive to the neurotoxiceffects of experimenter-administered binge doses of ethanol. However, less is known about age-related differencesin the neural consequences of self-administered ethanol.ΔFosB is a transcription factor that accumulatesafter chronic drug exposure and serves as a molecular marker of neural plasticity associatedwith the transition toaddiction.Weanalyzed the impact of chronic (18 two-bottle choice intake sessions spread across 42 days, sessionlength: 18 h) ethanol [or only vehicle (control group)] self-administration during adolescence or adulthood onthe induction of ΔFosB in several brain areas, anxiety-like behavior, and ethanol-induced locomotor activityand conditioned place preference (CPP) in Wistar rats. Adolescent rats exhibited a progressive escalation of ethanolintake and preference, whereas adult rats exhibited a stable pattern of ingestion. Few behavioral differencesin the open field or light-dark test were observed after the intake test. Furthermore, ethanol self-administrationdid not promote the expression of ethanol-induced CPP. There were, however, large age-related differences inthe neural consequences of ethanol drinking: a significantly greater number of ethanol-induced ΔFosB-positivecells was found in adolescents vs. adults in the prelimbic cortex, dorsolateral striatum, nucleus accumbens coreand shell, and central amygdala nucleus capsular and basolateral amygdala, with sex-related differences foundat central amygdala. This greater ethanol-induced ΔFosB induction may represent yet another age-related differencein the sensitivity to ethanol that may put adolescents at higher risk for problematic ethanol use.