Withaferin A attenuates Alcohol Abstinence Signs in Rats

Background: Withania somnifera (WS) have been reported to inhibit acquisition and expression conditioned place preference, self-administration and withdrawal anxiety of psychostimulants. In the present work, we have assessed the effect of withaferin A on somatic and affective symptoms of ethanol withdrawal syndrome in rats. Methods: Animals had given free access to ethanol uninterrupted for 21 days through liquid diet. Withaferin A (5, 10 and 20 mg/kg) was injected (ip) either during the development of ethanol dependence phase (days 15 – 21 or 30 min before ethanol withdrawal assessment. Withdrawal signs characterized by changes in somatic signs were measured in the open field followed by evaluation of anxiety parameters, locomotion, and depressive behavior. Results: Withaferin A treatment 30 min before 24 h postethanol withdrawal assessment did not alter the scores of somatic behavioral signs in ethanol abstinence animals. However, withaferin A (10 and 20 mg/kg, ip) from day 15-21 prevented the ethanol withdrawal-induced elevated scores of somatic behaviors, hyperlocomotion, depressive behavior, and anxiety. Withaferin A treatment did not influence the blood ethanol levels in dependent and withdrawn animals. However, withaferin A administration attenuated the elevated plasma corticosterone and ACTH levels in ethanol-withdrawn rats, suggesting withaferin A induced anti-stress effect and stabilization of HPA axis activity could have facilitated the inhibitory effect of withaferin A on ethanol withdrawal syndrome. Conclusion: The finding supports further investigation of withaferin A and other bioactive components of WS in alcohol addiction.