BAY 11-7085 ANDSU-6656 ATTENUATES ALCOHOL DEPENDENCE INDUCED SPONTANEOUS WITHDRAWAL SYNDROME LIKE HYPERALGESIA, CONVULSION AND DEPRESSION IN MICE

The present study has been designed to investigate the effect of SU6656, a selective inhibitor of src kinase and BAY 11-7085, a selective nuclear factor kappa B inhibitor, as potential target in a mouse model of spontaneous alcohol dependence induced withdrawal syndrome. Our experimental protocol consisted of administration of Alcohol (2 g/kg, 10%, v/v, oral), once daily for 7 days. Assessment of behavioral parameters and exploratory parameters was done on 7 day after 8 hr. of the last ethanol administration for a period of 120 minutes (90 minutes for behaviour and exploratory parameters and 30 minutes for depression and hyper responsiveness parameter). Ethanol withdrawal behaviors were hyper excitability (seizures) and this hyper excitability was behaviorally present in terms of super sensitivity to sub convulsive dose of PTZ (30 mg/kg, i.p) a convulsant. Withdrawal syndrome was quantitated in terms of a composite withdrawal severity score, exploratory behavior which was confirmed by, reflective of depression like behavior by force swim test, hyperalgesia by tail flick test. SU-6656 (1. 5 & 10 mg/kg, i.p.) and BAY 11-7085 (3. 10 & 30 mg/kg, i.p.)  treatment markedly and dose dependently (p<0.05) attenuated spontaneous alcohol withdrawal syndrome in mice measured in terms of withdrawal severity score, PTZ Kindling Seizures, hyperalgesia, depression. Thus, it is suggested that regulator of src kinase pathway and activation of nuclear factor kappa B pathway is involved in the development of alcohol withdrawal syndrome.