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

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ABSTRACT Early‐onset ethanol consumption predicts later development of alcohol use disorders. Age‐related differences in reactivity to ethanol's effects may underlie this effect. Adolescent rats are more sensitive and less sensitive… Click to show full abstract

ABSTRACT Early‐onset ethanol consumption predicts later development of alcohol use disorders. Age‐related differences in reactivity to ethanol's effects may underlie this effect. Adolescent rats are more sensitive and less sensitive than adults to the appetitive and aversive behavioral effects of ethanol, respectively, and more sensitive to the neurotoxic effects of experimenter‐administered binge doses of ethanol. However, less is known about age‐related differences in the neural consequences of self‐administered ethanol. &Dgr;FosB is a transcription factor that accumulates after chronic drug exposure and serves as a molecular marker of neural plasticity associated with the transition to addiction. We analyzed the impact of chronic (18 two‐bottle choice intake sessions spread across 42 days, session length: 18 h) ethanol [or only vehicle (control group)] self‐administration during adolescence or adulthood on the induction of &Dgr;FosB in several brain areas, anxiety‐like behavior, and ethanol‐induced locomotor activity and conditioned place preference (CPP) in Wistar rats. Adolescent rats exhibited a progressive escalation of ethanol intake and preference, whereas adult rats exhibited a stable pattern of ingestion. Few behavioral differences in the open field or light‐dark test were observed after the intake test. Furthermore, ethanol self‐administration did not promote the expression of ethanol‐induced CPP. There were, however, large age‐related differences in the neural consequences of ethanol drinking: a significantly greater number of ethanol‐induced &Dgr;FosB‐positive cells was found in adolescents vs. adults in the prelimbic cortex, dorsolateral striatum, nucleus accumbens core and shell, and central amygdala nucleus capsular and basolateral amygdala, with sex‐related differences found at central amygdala. This greater ethanol‐induced &Dgr;FosB induction may represent yet another age‐related difference in the sensitivity to ethanol that may put adolescents at higher risk for problematic ethanol use. HighlightsAdolescent, but not adult, rats exhibited escalation of ethanol intake.Ethanol intake induced &Dgr;FosB, particularly at AcbC, AcbSh, BLA and DMS.Adolescents exhibited greater &Dgr;FosB induction, compared to adults, at most areas.Females exhibited greater &Dgr;FosB induction, compared to males, at most areas.Adolescents and adults exhibited similar ethanol‐induced stimulation and anxiety.

Keywords: self administration; age related; ethanol; ethanol induced; dgr fosb

Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Year Published: 2017

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