Cholinergic Receptors and Addiction

Human behavior can be controlled by physical or psychological dependencies associated with addiction. One of the most insidious addictions in our society is the use of tobacco products which contain nicotine. This addiction can be associated with specific receptors in the brain that respond to the natural neurotransmitter acetylcholine. These nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels formed by the assembly of one or multiple types of nAChR receptor subunits. In this paper, we review the structure and diversity of nAChR subunits and our understanding for how different nAChR subtypes play specific roles in the phenomenon of nicotine addiction. We focus on receptors containing β2 and/or α6 subunits and the special significance of α5-containing receptors. These subtypes all have roles in regulating dopamine-mediated neurotransmission in the mesolimbic reward pathways of the brain. We also discuss the unique roles of homomeric α7 nAChR in behavioral responses to nicotine and how our knowledge of nAChR functional diversity may help guide pharmacotherapeutic approaches for treating nicotine addiction. While nicotine addiction is a truly global problem, the use of areca nut (betel) products is also a serious addiction associated with public health issues across most of South Asia, impacting as many as 600 million people. We discuss how cholinergic receptors of the brain are also involved with areca addiction and the unique challenges for dealing with addiction to this substance.