“When a person inhales smoke from a cigarette, nicotine is distilled from the tobacco and carried in the smoke particles into the lungs, where it is absorbed rapidly into the pulmonary venous circulation. It then enters the arterial circulation and moves quickly to the brain. Nicotine diffuses readily into brain tissue, where it binds to nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels. When a cholinergic agonist binds to the outside of the channel, the channel opens, allowing the entry of cations, including sodium and calcium. These cations further activate voltage-dependent calcium channels, allowing further calcium entry” (Benowitz, 2008). In the human brain, the most abundant nAChR subtype is the α4β2 nAChR (Benowitz, 2008). This nAChR subtype is reduced in the brains of patients suffering from AD (Okada et al., 2013) and is a crucial mediator for nicotine dependence (Benowitz, …show more content…
According to McGranahan, Patzlaff, Grady, Heinemann, and Booker (2011), global deletions of α4 or β2 subunits in mice lead to a lack of nicotinic reward exhibition. They conducted a study in which they discovered that it is the a4*-nAChR on dopaminergic neurons that is crucial for nicotinic reward in mice (McGranahan et al., 2011). In another study of the animal model of nicotine dependence, Tobey et al. (2012) found that the selective α4β2* nAChR antagonist “4-nitro-PFEB effectively blocks the reward-enhancing properties of nicotine that partly contribute to the initiation and maintenance of tobacco use” (Tobey et al., 2012). This shows that a relationship exists between α4β2* nAChRs and nicotine’s reward mechanism. Chronic desensitization of nAChRs due to repeated nicotine exposure leads to an increase in the number and function of nAChR binding sites in the brain (Benowitz, 2008). “It has been suggested that craving and withdrawal symptoms begin in chronic smokers when previously desensitized α4β2 nAChRs become unoccupied and recover to a responsive state during periods of abstinence, such as during nighttime sleep. Thus, nicotine binding and desensitization of