Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence
- Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA
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.
Keywords: nicotine, alcoholism, acetylcholine, nicotinic receptors, mesolimbic dopamine system
Citation: 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
Received: 29 January 2013; Accepted: 16 April 2013;
Published online: 30 April 2013.
Edited by:Nicholas W. Gilpin, Louisiana State University Health Sciences Center New Orleans, USA
Reviewed by:Shaolin Wang, University of Virginia, USA
Darlene H. Brunzell, Virginia Commonwealth University, USA
Shafiqur Rahman, South Dakota State University, USA
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.
*Correspondence: Andrew R. Tapper, Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA. e-mail: firstname.lastname@example.org