Biochemistry & Pharmacology: Open Access
Open Access

Abstract

Nicotinic Acetylcholine Receptors in the Ventral Segmental Area are Important Targets for Nicotine and Ethanol Co-dependence

Devin H. Taylor, Scott C. Steffensen and Jie Wu

Tobacco and alcohol are the most commonly abused drugs. The nicotine (NIC) in tobacco and the ethanol (EtOH) in alcoholic drinks are responsible for their dependence respectively. The magnitude of tobacco smoking is drastically higher among alcoholics, suggesting a NIC-EtOH co-dependence. However, the mechanisms of NIC-EtOH interaction are not fully known, and the clarification of this action is clinically relevant. The majority of the NIC-EtOH interaction utilizes the ventral tegmental area (VTA) through both dopamine (DA) and non-DA systems. EtOH has been shown to bind directly to some nicotinic acetylcholine receptors (nAChRs) as, of course, does NIC. The non-selective/noncompetitive
nAChR antagonist mecamylamine (MEC) has been shown to partially block the DA releasing action of EtOH in the nucleus accumbens (NAc), while both the α4β2 nAChR antagonist dihydro-β-erythroidine (DHβE) and the α7 nAChR antagonist methyllycaconitine (MLA) do not. However, the α6-containing nAChRs (α6*-nAChRs) are responsible for both NIC-induced effects on DA release in the NAc and EtOH-induced GABA release in the VTA, suggesting that the α6*-nAChRs likely play a significant role in NIC-EtOH interactions. In this review, we have summarized current studies that reveal how EtOH reward through VTA nAChRs and what nAChR subtypes play roles in mediation of EtOH’s effects
in mesolimbic circuits. The accumulating lines of evidence suggest that the nAChRs, especially α6*-nAChRs in the VTA are likely important targets for NIC-EtOH interactions and NIC-EtOH co-dependence.