Exploring Novel Pharmacological Approaches to Attenuate Experimental Alcohol Dependence induced Withdrawal Syndrome in Mice

Abstract

The present study has been designed to investigate the effect of BAY 11-7085, a selective nuclear newlinefactor kappa B inhibitor and investigate the effect of SU6656, a selective inhibitor of src kinase as newlinepotential target on the development of alcohol dependence in a mouse model of spontaneous newlinewithdrawal syndrome. Our experimental protocol consisted of administration of Alcohol (2 g/kg, newline10%, v/v, oral), once daily for 7 days. Assessment of behavioral parameters and exploratory newlineparameters was done on 7 day after 8 hr. of the last ethanol administration for a period of 120 newlineminutes (90 minutes for behaviour and exploratory parameters and 30 minutes for depression, newlineanxiety and hyper responsiveness parameter). Ethanol withdrawal behaviors were hyper excitability newline(seizures) and this hyper excitability was behaviorally present in terms of super sensitivity to sub newlineconvulsive dose of PTZ (30 mg/kg, i.p) a convulsant. Withdrawal syndrome was quantitated in terms newlineof a composite withdrawal severity score, Teeth chattering, Rearing frequency, Head nodding, Wall newlineclimbing test, exploratory behavior which was confirmed by locomotor activity (LCA) in open field newlinetest, reflective of depression like behavior by force swim test, anxiety by elevated plus test, newlinehyperalgesia by tail flick test. BAY 11-7085 (3. 10 and 30 mg/kg, i.p.) and SU-6656 (1. 5 and 10 newlinemg/kg, i.p.) treatment markedly and dose dependently (plt0.05) attenuated spontaneous alcohol newlinewithdrawal syndrome in mice measured in terms of withdrawal severity score, wall climbing, newlinelocomotor sensitization by open field test, hyperalgesia, anxiety and depression. Thus, it is suggested newlinethat activation of nuclear factor kappa B pathway and src kinase pathway is involved in the newlinedevelopment of alcohol withdrawal syndrome. newline