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Review
.2010 Jul;15(3):250-65.
doi: 10.1111/j.1369-1600.2010.00213.x. Epub 2010 Apr 29.

Cognitive effects of nicotine: genetic moderators

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Review

Cognitive effects of nicotine: genetic moderators

Aryeh I Herman et al. Addict Biol.2010 Jul.

Abstract

Cigarette smoking is the main preventable cause of death in developed countries, and the development of more effective treatments is necessary. Cumulating evidence suggests that cognitive enhancement may contribute to the addictive actions of nicotine. Several studies have demonstrated that nicotine enhances cognitive performance in both smokers and non-smokers. Genetic studies support the role of both dopamine (DA) and nicotinic acetylcholine receptors (nAChRs) associated with nicotine-induced cognitive enhancement. Based on knockout mice studies, beta2 nAChRs are thought to be essential in mediating the cognitive effects of nicotine. alpha7nAChRs are associated with attentional and sensory filtering response, especially in schizophrenic individuals. Genetic variation in D2 type DA receptors and the catechol-O-methyltransferase enzyme appears to moderate cognitive deficits induced by smoking abstinence. Serotonin transporter (5-HTT) gene variation also moderates nicotine-induced improvement in spatial working memory. Less is known about the contribution of genetic variation in DA transporter and D4 type DA receptor genetic variation on the cognitive effects of nicotine. Future research will provide a clearer understanding of the mechanism underlying the cognitive-enhancing actions of nicotine.

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Figure 1
Figure 1
A cartoon illustrating the hypothesized effects of nicotine on the regulation of dopamine (DA), glutamate and acetylcholine (ACh) release in the prefrontal cortex (PFC), a region thought to be essential in mediating cognitive enhancement from nicotine. Nicotine enhances the release of glutamate and DA, which leads to increased Ach release and the potential activation of presynaptic glutamate and DA receptors on cholinergic terminals. The type and exact location of these receptors remains to be elucidated. See (Briand et al., 2007; Parikh et al., 2008; Sarter et al., 2009) for details.
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