Nicotinic Acetylcholine Receptors Containing the α4 Subunit Modulate Alcohol Reward

Liu, Liwang; Hendrickson, Linzy M.; Guildford, Melissa J.; Zhao-Shea, Rubing; Gardner, Paul; Tapper, Andrew R.

doi:10.1016/j.biopsych.2012.09.019

Cited by 54 publications

(56 citation statements)

References 45 publications

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“…Focusing on alcohol, animal models have demonstrated that nicotinic receptor genes moderate the ethanol-induced release of dopamine (Soderpalm et al, 2000; Larsson et al, 2005) and ethanol may also interact directly with the function of nAChRs (Wood et al, 1995; Liu et al, 1994). In particular, animal studies of nicotinic receptors containing the alpha 4 subunit have shown a significant relationship with the reward response to alcohol (Liu et al, 2013) and to alcohol withdrawal (Butt et al, 2004). Further evidence is provided in recent animal studies of varenicline, an alpha4-beta2 nicotinic receptor partial agonist used in smoking cessation.…”

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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“…On the other hand, alcohol can also increase acetylcholine release into the ventral tegmental area (Larsson et al, 2005), driving activation of DA neurons through nAChRs. In this regard, a role of α4 nAChR subunits in alcohol reward has been proposed (Liu et al, 2013). It has also been shown that nicotine may increase alcohol’s reinforcing properties via upregulation of nAChRs, thus setting the condition for enhanced vulnerability to consume alcohol (Hendrickson et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Varenicline decreases nicotine but not alcohol self-administration in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats

Scuppa

Cippitelli

Toll

et al. 2015

Drug and Alcohol Dependence

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Background Alcohol and nicotine are largely co-abused. Here, we investigated whether concurrent exposure to both addictive drugs influences each other’s consumption and whether varenicline attenuates alcohol consumption in the presence of nicotine. Methods Marchigian Sardinian alcohol-preferring (msP) rats trained to simultaneously self-administer oral alcohol (10% v/v) and intravenous nicotine (30 μg/kg/inf.) were used. Additional groups of rats were trained to self-administer either alcohol or nicotine. Further, msP rats were also trained to self-administer nicotine followed by 22-h/day access to alcohol and water in a two bottle free choice paradigm or water alone. The effects of varenicline (0.0, 0.3, 1.0, 3.0 mg/kg, p.o.) on alcohol and nicotine consumption was tested. Results In a self-administration paradigm, msP rats showed a significantly high levels of alcohol and nicotine intake when the drugs were administered alone. However, when access to both drugs occurred concomitantly, the number of nicotine infusions self-administered was significantly decreased. Nicotine self-administration was markedly reduced by varenicline regardless of whether it was self-administered alone or concurrently with alcohol. In a two bottle choice test, varenicline significantly decreased nicotine self-administration but had no influence on alcohol consumption. Conclusion Varenicline is highly efficacious in decreaasing nicotine self-administration either alone or in combination with alcohol. However, varenicline failed to influence both operant responding for alcohol and home-cage alcohol drinking in msP animals. Taken together, our findings suggest that the effects of varenicline could be specific to nicotine under conditions where excessive alcohol drinking is facilitated by genetic factors as in msP rats.

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“…11,26 Similarly, ethanol-related behavior and ethanol-induced midbrain dopaminergic function get decreased in β4 KO mice. 55 On the other hand, β2 KO mice behave similar to WT type mice in ethanol drinking behaviors. 56 In addition, β6 KO and β3 KO mice also display ethanol drinking behavior that is similar to WT mice in a two-bottle ethanol drinking paradigm.…”

Section: Knockout and Transgenic Models And Nachrsmentioning

confidence: 97%

“…55,59–66 For example, systemic or local administration of nAChR ligands reduce ethanol drinking in a number of animal models. 32,60,61,65 Furthermore, nAChRs in the ventral tegmental area (VTA) regulate ethanol consumption and associated mesolimbic neurochemical effects (e.g., dopamine release in the nucleus accumbens (Acb)), as shown in various preclinical studies.…”

Section: Knockout and Transgenic Models And Nachrsmentioning

confidence: 99%

Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism

Rahman

Engleman

Bell

2016

Progress in Molecular Biology and Translational Science

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Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic–cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions.

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Nicotinic Acetylcholine Receptors Containing the α4 Subunit Modulate Alcohol Reward

Cited by 54 publications

References 45 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

Varenicline decreases nicotine but not alcohol self-administration in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats

Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism

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