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

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Nicotine dependence (ND) is one of the world's 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.

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

Document Type: Research Article

Publication date: 2011-01-01

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