Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence
Student Authors
Melissa Guildford DernerLinzy Hendrickson
Academic Program
NeuroscienceUMass Chan Affiliations
Tapper LabDepartment of Psychiatry
Brudnick Neuropsychiatric Research Institute
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2013-04-30Keywords
Receptors, NicotinicSubstance-Related Disorders
Mental Disorders
Psychiatry
Psychiatry and Psychology
Substance Abuse and Addiction
Metadata
Show full item recordAbstract
Alcohol and nicotine are often co-abused. As many as 80-95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence.Source
Hendrickson LM, Guildford MJ and Tapper AR (2013) Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence. Front. Psychiatry 4:29. doi: 10.3389/fpsyt.2013.00029 Link to article on publisher's site
DOI
10.3389/fpsyt.2013.00029Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30395PubMed ID
23641218Related Resources
Rights
Copyright: © 2013 Hendrickson, Guildford and Tapper. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.ae974a485f413a2113503eed53cd6c53
10.3389/fpsyt.2013.00029