Effects of restraint stress on alcohol consumption in adolescent rats

WILLE-BILLE, ARANZA; PAUTASSI R.M.

Río de janeiro

Congreso; 9th IBRO World Congress of Neuroscience; 2015

INTERNATIONAL BRAIN RESEARCH ORGANIZATION

Effects of restraint stress on alcohol consumption in adolescent rats.Adolescence is a developmental stage associated with neurobiological, behavioral and hormonal changes. These changes may underlie the greater vulnerability to drug abuse observed during this stage. Preclinical studies suggest that adolescents are uniquely sensitive to ethanol´s pharmacological effects and that this pattern of response may put them at risk for alcohol initiation and escalation. Adolescent rats exhibit, when compared to adults, greater sensitivity to the appetitive and social facilitating effects of ethanol; yet they are less sensitive than adults to the aversive motivational effects of the drug. Stress is one of the risk factors that promotes greater engagement and escalation into alcohol consumption. Stress can enhance the appetitive reinforcing and decrease the aversive effects of ethanol; and it has been demonstrated that adolescents are more sensitive to the anxiolytic effects of alcohol than adults. Based on this background, we aimed at analyzing the permissive effects of stress on alcohol intake, in adolescents; and scrutinize possible sex-differences in this effect. Male and female rats, 30 days-old, were subjected to five daily sessions of 120 minutes of restraint stress, using PVC tubes 20 cm long and 5-8 cm wide. Forty-eight hours later the alcohol intake test began. The two-bottle choice alcohol intake test lasted 2 weeks, with intermittent, every-other day access to the drug (18 hours per day, three times a week) taking. Alcohol solutions were ethanol 4% v/v on the first week, and 5% v/v on the second; in both cases accompanied with a bottle of vehicle (tap water). We registered g/kg alcohol consumed and percent preference. The hypothesis was that stress would exacerbate alcohol consumption, probably because of the alterations in the anxiety response and in the tone of HPA axis.The results indicated, for both g/kg and percent preference ethanol ingested, an interactive effect between sex and stress (F1,24=17,83; F1,24=17,53; ps < 0,001; for g/kg and percent preference, respectively), with higher alcohol intake in stressed females than in their control counterparts. Males were unaffected by stress. There were no differences across conditions in the total amount of fluids consumed.The relationship found in females between stress and subsequent alcohol consumption, guides to further analysis of the molecular basis underlying this permissive effect. Future experiments will assess potential pharmacological treatment to mitigate these consequences of stress. Specifically, we will employ pretreatment with antagonists of kappa opioid receptor and CRH1 receptors.