Basal Anxiety Negatively Correlates with Vulnerability to Ethanol-Induced Behavioral Sensitization in DBA/2J Mice: Modulation by Diazepam

BackgroundAnxiety disorders predispose individuals to the development of alcohol dependence in humans. Surprisingly, whether anxiety is a trait influencing the development of alcohol-related behaviors in rodents remains controversial. Here, we addressed the hypothesis of a relationship between basal anxiety levels and the development of ethanol (EtOH)-induced behavioral sensitization (EIBS), a model of neuroadaptations occurring after repeated EtOH exposure which is proposed to play a role in early and recurring steps of addiction. MethodsEtOH-naive DBA/2J mice were submitted to the elevated plus maze and light/dark box tests to evaluate their basal anxiety levels. Then, mice received daily intraperitoneal injection of saline or 2g/kg EtOH for 10days and locomotor activity was immediately monitored. Mice were then split into resistant and sensitized phenotypes based on their increase in locomotion. The relationship between basal anxiety and the development of sensitization was investigated. In addition, we tested the effect of an 8-day-long treatment with 4mg/kg diazepam, a broad-spectrum benzodiazepine anxiolytic, on the expression of sensitization in both resistant and sensitized mice. ResultsFor the first time, we showed that vulnerability to EIBS is negatively correlated with basal anxiety. Moreover, a diazepam treatment during EIBS procedure increased EtOH-induced hyperlocomotion of resistant mice after 1week of withdrawal (but not immediately after) without any effect in the group of sensitized mice. ConclusionsThis study shows that, in mice, basal anxiety predicts the vulnerability to EIBS. Mice exhibiting low basal anxiety will develop higher EIBS than mice with elevated anxiety levels. Modulation of anxiety by a diazepam treatment during the development of EIBS enhances its expression after 1week postinduction. Altogether, we demonstrated an inverse relationship between basal anxiety-like behaviors and EIBS vulnerability and that resistance to EIBS vanishes after anxiolytic treatment.