Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals.

Abstract Ethnopharmacological relevance Withania somnifera (L.) Dunal (WS), a known ‘Rasayana’ (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. Among its other uses, WS is specifically recommended in Ayurveda for central nervous system related disorders. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies. Aim of the study To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas. Methodology Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1,: 1 -distilled water, 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6–8 days). Effect of WS on reinstating behaviour of rats (time spent in alcohol paired compartment) primed with alcohol injection was noted. Effect of WS (450 mg/kg/) on GABA and dopamine levels from rat midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 30) following the first phase of standardisation assay. The rats (n = 24) were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. Levels were measured on Day 16. Results WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone but it differed significantly from control (p  Conclusion Withania somnifera protected animals from relapse and showed beneficial effects on the neurotransmitters implicated in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.