Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence

Authors: Jie Wu, Ming Gao, Devin H Taylor
DOI: 10.1038/aps.2013.181


Jie WU1, 2, *, Ming GAO2, Devin H TAYLOR2
1Ningbo University Medical School, Ningbo 315211, China; 2Division of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph’s Hospital and Medical Center, Phoenix, Arizona 85013–4409, USA

Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH’s effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol’s abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.

Keywords: alcoholism; abused substance; ethanol reward and dependence; smoking; nicotine; nicotinic acetylcholine receptor; mesolimbic dopamine system

* To whom correspondence should be addressed.
Received 2013-10-07 Accepted 2013-12-18

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