Alcohol addiction affects a broad range of populations and has serious socio-economic and health implications for third-world countries including Pakistan. Currently, available therapies have serious challenges regarding their safety, efficacy, and tolerability leading to a high degree of relapse. Alcohol causes significant central and peripheral neurotoxicity leading to depression, Hyperalgesia and allodynia that significantly contributes to the affective component of withdrawal and are major contributor of relapse. There is growing evidence of the role of the spino-bulbar-cerebellar pathway in the expression of hyperalgesia and allodynia. The spino-bulbar-cerebellar pathway Serotonergic and adenosinergic neuron’s role in processing and control of Alcohol withdrawal-induced hyperalgesia and as a potential drug target has not yet been explored. Recently some plant origin compounds have been documented to reverse behavioral effects of alcohol sensitization through adenosinergic and serotonergic modulation. The project aims to investigate the potential of selected natural pure Phytochemicals, with documented neuroprotective effects, on acquisition and expression of alcohol dependence using animal models focusing adenosine and serotonin turnover in spino-bulbar-cerebellar pathway.

The specific objectives are to explore the effects of various doses of selected Phytochemicals on acquisition and expression of Alcohol withdrawal syndrome, Alcohol withdrawal induced depression, Alcohol withdrawal induced hyperalgesia and Allodynia, Alcohol withdrawal induced Cognitive decline and Alcohol withdrawal induced anxiety and Alcohol withdrawal induced altered socialization using animal model of alcohol addiction. At the end of the behavioral experiments’ mice shall be sacrificed key brain areas like striatum, nucleus accumbens, Hippocampus, and spino-bulbar-cerebellar pathway shall be excised and shall be screened for changes in serotonin, adenosine, and its metabolites levels along with receptors densities using specified monoclonal antibodies.

 These phytochemicals already in use can help repurpose these new potential phytochemicals as an alternative therapy for harm reduction in alcohol addiction which is the growing, least recognized health challenge in Pakistan.