Shared genes influence sensitivity to the effects of ethanol on locomotor and anxiety-like behaviors, and the stress axis

Abstract.

Rationale: In rodents, a common response to many drugs of abuse, including ethanol (EtOH), is locomotor stimulation. It has been proposed, although debated, that EtOH-induced locomotor stimulation may represent an animal model of EtOH's euphoric effects. Another possibility is that this behavioral phenotype may represent an altered state of anxiety, and/or stress axis activation. Objectives: Mouse lines selectively bred for sensitivity (FAST) or resistance (SLOW) to EtOH's low dose locomotor stimulant effects were tested for differential sensitivity to EtOH's anxiolytic and/or stress axis activating effects, with the goal of detecting genetic correlations. Methods: Saline- and EtOH-treated FAST and SLOW mice were tested on the elevated plus maze and the light-dark box, two widely used measures of anxiety-related behavior in rodents. In addition, serum corticosterone (CORT) levels were measured at various time points following injection of saline or ethanol. Results: Behavioral data from both anxiety tests showed that FAST mice were less sensitive to EtOH's anxiolytic effects than were SLOW mice. Moreover, late recovery of elevated serum CORT levels following mild saline injection stress, as well as reduced CORT release in response to EtOH, suggested that FAST mice may possess a less responsive stress axis. Conclusions: These results provide evidence that sensitivity to the effects of EtOH on locomotor behavior, anxiety-like behavior, and the stress axis share some genetic influence.