Review: Nicotinic receptors and stages of nicotine dependence

Abstract

Smoking is one of the leading causes of preventable death, where nicotine has been identified as the primary addictive constituent of tobacco. Consequently, there have been extensive investigations into the neuroadaptations that occur as nicotine dependence develops, where numerous neurological systems have been implicated. The focus of this review was on nicotinic acetylcholine receptor neuroadaptations that occur during the development of nicotine dependence. This focus was selected because (1) the nicotinic receptors are the primary binding sites for both nicotine and the most efficacious pharmacological smoking cessation treatments and (2) the receptors are located throughout the brain with considerable neuromodulatory ability. However, there was difficulty associated in outlining the role of nicotinic receptors in the development of nicotine dependence because it comprises a series of stages involving different neurological systems rather than a single state. To address this issue, the review adopts a novel approach and considers the role of nicotinic receptor subtypes at separate stages of the nicotine dependence cycle. This information was then used to examine the nicotinic receptor-related therapeutic mechanisms of three main pharmacological smoking cessation treatments.

Nicotine ameliorates cognitive deficits induced by maternal LPS exposure: A study in rats

“…As aforementioned, Yu et al (2010) found no enhancing effect of nicotine (0.15 or 0.5 mg/kg, subcutaneously) in mice that had been prenatally exposed to maternal infectious agents. However, a single injection of nicotine was administered to model an acute effect as opposed to repeated nicotine treatment, which leads to different neurochemical alterations (Brennan et al, 2010), and therefore might affect cognitive performance differently.…”

“…The importance of the cholinergic system and nAChRs in mediating cognitive processes has been observed across multiple species (Klinkenberg et al, 2011; Wallace and Porter, 2011; Rezvani and Levin, 2001), and improvements in humans have been shown in domains relevant to schizophrenia, such as sensorimotor gating (Postma et al, 2006; Woznica et al, 2009), attention (Barr et al, 2008; Hahn et al, 2012), memory (Jubelt et al, 2008) and executive control (Petrovsky et al, 2013). Neuronal α7 receptors, for example, exist at pre- and post-synaptic locations; thus, they can rapidly mediate synaptic transmission and plasticity, as well as neurotransmitter release that is relevant to cognitive functioning, such as that of acetylcholine, dopamine, glutamate, serotonin and GABA (Benowitz, 2009; Brennan et al, 2010). …”

Effects of chronic nicotine, nicotine withdrawal and subsequent nicotine challenges on behavioural inhibition in rats

“…With increasing research suggesting potential roles of other nAChRs subtypes in nicotine addiction (e.g. β3, β4, α4 and α6) (see Brennan et al 2010;Penton and Lester 2009 for reviews), it is important that future research begins to determine the extent to which these receptors may also be involved in the nicotine-induced impulsivity. Figure 1 clearly shows a gradual strengthening (i.e.…”

High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness

“…As discussed above, chronic exposure to nicotine in tobacco alters nAChR levels in the human brain, and this may contribute to the development of nicotine dependence (Staley et al 2006). A large number of studies have identified the nAChR subtypes, and critical brain circuits responsible for the addictive effects of nicotine, in particular, the ability of nAChRs in the ventral tegmental area to drive dopamine release and support nicotine reinforcement (reviewed in: Brennan et al 2010; Buisson and Bertrand 2002; Changeux 2010; Govind et al 2009). Nicotine dependence is also co-morbid with other substance abuse disorders, including addiction to cocaine, alcohol, cannabinoids, and opiates (Tuesta et al 2011).…”