Nicotinic receptors as therapeutic targets for drug addictive disorders.

Drug addiction is a chronic neuropsychiatric disorder which is characterized by a compulsion to take drugs and loss of control in limiting intake. The worldwide impact of drug addiction on morbidity and mortality is very high. Evidence from preclinical and clinical studies suggests that brain nicotinic acetylcholine receptors (nAChRs), play a critical role in various addictive disorders, including nicotine addiction and alcoholism. Thus, there is an increasing impetus in developing new therapeutics for addictive disorders by targeting brain nAChRs. This review highlights the important preclinical findings involving nAChR ligands in regulating nicotine, alcohol and other addictive drug-induced neurobiological changes in animal models and humans. A number of partial agonists or antagonists targeting nAChRs have shown therapeutic benefit in nicotine addiction and alcohol use disorders are also discussed. Furthermore, the role of nAChRs in other addictive disorders is reviewed. Overall, novel pharmacological agents that target brain nAChRs for future drug development are discussed.