Impact of Genetic Variability in Nicotinic Acetylcholine Receptors on Nicotine Addiction and Smoking Cessation Treatment

P.      Russo; A.      Cesario; S.      Rutella; G.      Veronesi; L.      Spaggiari; D.      Galetta; S.      Margaritora; P.      Granone; D.      S. Greenberg

doi:10.2174/092986711793979715

Abstract

Nicotine dependence (ND) is one of the worlds leading causes of preventable death. Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the world. Evidence for a genetic influence on smoking behaviour and ND has prompted a search for susceptibility genes. Evidence has recently accumulated that single nucleotide polymorphisms (SNPs) in the genetic region encoding the nicotinic acetylcholine receptor (nAChR) subunits α6, α5, α3, and β4 are associated with smoking and ND. Brain nAChR are a heterogeneous family of ion channels expressed in the various parts of the brain. A number of studies suggest that brain nAChR are critical targets for the development of pharmacotherapy for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their function in response to endogenous brain transmitters, and how their functions are regulated in the presence of nicotine. Additionally, we will provide an overview of the three major pharmacotherapies for smoking cessation (which have demonstrated efficacy) such as: nicotine replacement therapy (NRT), bupropion, and varenicline. An appreciation of the complexity of nAChR and their regulation will be necessary for the development of nAChR modulators as potential pharmacotherapy for drug addiction. Prevention strategies should be tailored to carriers of SNPs located on chromosome 15q and that are strongly associated with nicotine dependence and risk of lung cancer.

Keywords: Nicotine-addiction, genetic variants, nicotinic receptor, varenicline, bupropion, Smoking Cessation Treatment, nicotine, neurobiology, Mental Disorders, drug addiction, sensitization, solubility, intoxication, frustration, anger, anxiety, insomnia, decreased heart rate, appetite, neuroadaptation, dose, Brain Stress Systems, stress, homeostasis, anxiolytic, organic alkaloid, aromatic amines, pyrrolidine ring, cholinergic receptors, pulmonary alveolar capillary, venous circulation, extraneuronal cholinergic system, inflammatory responses, absorption, extraneuronal cholinergic, sarcoidosis, tumour, epithelial cells, parkinsonian symptoms, placebo, Neurochemistry, ion channels, Agonist, Antagonist, allosteric receptors, isomerization, Alzheimer's disease, aging, cholinergic axons, neurons, locus coeruleus, acetylcholine-secreting neurons, psychopharmacological consequences, microRNA, adolescence, transdermal patch, oral inhaler, lozenges, autocrine-proliferative, alkaloid cytisine, nausea, agitation, aspartic acid, polymorphisms, primary care physicians, heterogeneity