Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

Tapper, Andrew R.; McKinney, Sheri; Nashmi, Raad; Schwarz, Johannes; Deshpande, Purnima; Labarca, Cesar; Whiteaker, Paul; Marks, Michael J.; Collins, Allan C.; Lester, Henry A.

doi:10.1126/science.1099420

Cited by 648 publications

(643 citation statements)

References 23 publications

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“…Similar associations between CHRNA4 and nicotine dependence have been reported in studies of adults (Feng et al 2004; Li et al, 2005; Breitling et al, 2009). Several studies have also demonstrated associations between CHRNA4 and subjective effects of nicotine (Picciotto et al, 1998; Tapper et al, 2004). Many of these associations involve high frequency SNPs within the same LD bins measured in this study, including rs1044396 and rs2236196.…”

Section: Discussionmentioning

confidence: 99%

Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

Coon

Piasecki

Cook³

et al. 2014

Alcoholism Clin & Exp Res

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Background Binge drinking is responsible for over half of all alcohol-related deaths, and results in significant health and economic costs to individuals and society. Knowledge of genetic aspects of this behavior, particularly as it emerges in young adulthood, could lead to improved treatment and prevention programs. Methods We have focused on the association of variation in neuronal nicotinic receptor subunit genes (CHRNs) in a cohort of 702 Hispanic and non-Hispanic White young adults who are part of the Social and Emotional Contexts of Adolescent Smoking Patterns (SECASP) study. Fifty-five single nucleotide polymorphisms covering the variation in five CHRNs (CHRNA4, CHRNB2, CHRNA2, CHRNB3A6 and CHRNA5A3B4) were studied. Results Frequency of binge drinking and other correlated alcohol consumption measures were significantly associated with SNPs in CHRNA4 (p-values ranged from 0.0003 to 0.02), but not with SNPs in other CHRNs. This association was independent of smoking status in our cohort. Conclusions Variants in CHRNA4 may contribute to risk for binge drinking in young adults in this cohort. Results will need to be confirmed in independent samples.

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Section: Discussionmentioning

confidence: 99%

Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

Coon

Piasecki

Cook³

et al. 2014

Alcoholism Clin & Exp Res

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“…132 Both subunits are upregulated by chronic nicotine treatment and their absence in knockout mice results in a lack of nicotine selfadministration and nicotine-induced dopamine release in the VTA. [132][133][134][135] Tapper et al 136 genetically altered the a 4 -subunit to make it hypersensitive; low doses of nicotine that selectively activate nAChRs containing these mutated subunits produced reinforcement, tolerance and sensitization without having such effects in wild-type mice. CHRNA4 encodes the a 4 subunit, and several genetic variants have been associated with smoking.…”

Section: Cholinergic Receptorsmentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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“…26 The possible candidate genes still include genes involved in the dopamine, norepinephrine or serotonin pathways as well as in nicotinic acetylcholine receptors expression. [27][28][29][30] Further progress will thus need larger genomic studies, taking into account new polymorphisms in various candidate genes together with phenotyping and behavioural studies.…”

Section: Gene Polymorphisms and Tobacco Consumptionmentioning

confidence: 99%

Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort

Gambier

Marie

et al. 2005

Pharmacogenomics J

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This study was designed in order to investigate the influence of the genetic polymorphism of CYP2A6 on the amount of smoking. In all, 463 French adults included in the Stanislas cohort were studied and underwent two examinations at 5 years distance (t 0 and t þ 5 years). Information on their smoking habits was collected. They were genotyped by RFLP for the CYP2A6*1A, CYP2A6*1B and CYP2A6*4 alleles. CYP2A6*1B and CYP2A6*4 allele frequencies were 32 and 4%, respectively. The subjects carrying the CYP2A6*1B allele oxidize nicotine to cotinine faster than subjects with the CYP2A6*1A allele. The number of cigarettes smoked per day was significantly higher in the CYP2A6*1B/*1B group as compared to the CYP2A6*1A/*1A group (P ¼ 0.01 at t 0 ; P ¼ 0.001 t þ 5 years), with a larger increase in their daily cigarettes consumption over the 5-year period (P ¼ 0.006). No significant difference in the smoking status was observed according to the CYP2A6 genotype. These data suggest that the CYP2A6*1B is associated with the number of cigarettes smoked per day.

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Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

Cited by 648 publications

References 23 publications

Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

Association of the CHRNA4 Neuronal Nicotinic Receptor Subunit Gene with Frequency of Binge Drinking in Young Adults

Overview of the pharmacogenomics of cigarette smoking

Association of CYP2A6*1B genetic variant with the amount of smoking in French adults from the Stanislas cohort

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