RESUMO
Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S0 generation and filial generations 1 (S1), S2, and S3 of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S1-ADHI but not S1-ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/fisiopatologia , Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Predisposição Genética para Doença , Estresse Psicológico/fisiopatologia , Fatores Etários , Animais , Ansiedade/genética , Depressores do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Etanol/administração & dosagem , Feminino , Masculino , Fenótipo , Ratos , Ratos Wistar , Assunção de Riscos , Seleção Artificial , Estresse Psicológico/complicaçõesRESUMO
Adolescents may be more sensitive to stress-induced alcohol drinking than adults, which would explain the higher prevalence of alcohol abuse and dependence in late adolescence than in adulthood. The present study analyzed the impact of restraint stress on the initiation of alcohol intake across 2 weeks of intermittent, two-bottle choice intake in male and female adolescent rats and adult female rats. Restraint stress significantly increased alcohol intake and preference in female adolescent rats but decreased alcohol intake and preference in male adolescent and female adult rats. The effects of restraint stress on alcohol intake were mitigated in adolescent females following administration of the κ opioid receptor antagonist norbinaltorphimine. Adolescent but not adult female rats that were subjected to restraint stress spent more time on the open arms of the elevated plus maze. Female adolescents exposed to stress also exhibited greater risk-taking behaviors in a concentric square field test compared with non-stressed controls. These results indicate age- and sex-related differences in the sensitivity to alcohol-stress interactions that may facilitate the initiation of alcohol use in female adolescents. The facilitatory effect of stress on alcohol intake was related to greater exploratory and risk-taking behaviors in young females after stress exposure.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Caracteres Sexuais , Estresse Psicológico/fisiopatologia , Envelhecimento/efeitos dos fármacos , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Comportamento de Escolha/efeitos dos fármacos , Comportamento de Escolha/fisiologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos Wistar , Receptores Opioides kappa/antagonistas & inibidores , Receptores Opioides kappa/metabolismo , Restrição Física , Assunção de Riscos , Estresse Psicológico/tratamento farmacológicoRESUMO
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. ΔFosB 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 42days, session length: 18h) ethanol [or only vehicle (control group)] self-administration during adolescence or adulthood on the induction of ΔFosB 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 ΔFosB-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 ΔFosB induction may represent yet another age-related difference in the sensitivity to ethanol that may put adolescents at higher risk for problematic ethanol use.