Anxiety and sensitivity to ethanol and pentobarbital in alcohol withdrawalseizure-prone and withdrawal seizure-resistant mice

Background: Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice were selectively bred for high and low handling-induced convuls ions, respectively, after chronic ethanol treatment. Withdrawal severity is one factor that may contribute to the development of alcoholism and/or sub stance abuse, and anxiety is another. We sought to explore whether these fa ctors are genetically related. Methods: WSP and WSR mice of two replicate pairs of selected lines were tes ted for anxiety-related behaviors on the canopy stretched-attend-posture ap paratus 20 min after intraperitoneal injection of ethanol (2 g/kg, 20% v/v) , pentobarbital (20 mg/kg), or an equivalent volume of saline. Dependent me asures of anxiety included number of stretched attend postures (SAP) and ti me spent in the exposed area of the apparatus. Number of line crossings, wh ich measures overall activity, was also scored. Results: WSP mice given saline exhibited more SAP than WSR mice given salin e, which indicated greater baseline anxiety. Ethanol and pentobarbital both reduced SAP and increased time spent in the exposed area of the apparatus, which indicated that both drugs exerted an anxiolytic effect. Despite base line differences in SAP between selected lines, both anxiolytic drugs reduc ed SAP to similar levels in WSP and WSR mice. Conclusions: These results support the hypothesis that WSP mice are more se nsitive than WSR mice to the anxiety-reducing effects of ethanol and pentob arbital. Some genes that influence this difference are likely to be the sam e as those that influence ethanol withdrawal severity. Thus, higher basal a nxiety and greater genetic sensitivity to anxiolytic drug effects may relat e to a greater genetic predisposition to the development of severe alcohol withdrawal signs.