Nicotine and Behavioral Sensitization

Abstract

Use of tobacco products contributes to hundreds of thousands of premature deaths and untold millions of dollars in health care costs in this country each year. Nicotine is the principal neuroactive component in tobacco, but, despite ongoing research efforts, the cellular basis of its effects on behavior remains unclear. Efforts to resolve this conundrum have focused on the mesoaccumbens dopamine system, which contributes to the rewarding effects of many addictive drugs, including nicotine. The goal of this review is to outline recent advances and highlight some of the important unanswered questions regarding nicotine's effects on neuronal excitability and synaptic plasticity within the brain reward pathways.

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

“…There is a consensus that up-regulation of ␣4␤2* nAChRs is primarily controlled at the post-transcriptional level, with little change in ␣4 or ␤2 nAChR mRNA levels (Marks et al, 1992). Various mechanisms have been proposed to explain nicotine-mediated up-regulation Buccafusco et al, 2009;Benowitz, 2010;Changeux, 2010b;Mao and McGehee, 2010). One hypothesis is that the initial receptor desensitization contributes to upregulation, possibly via receptor phosphorylation (Léna and Changeux, 1993;Swope et al, 1999;Wiesner and Fuhrer, 2006).…”

Nicotinic Regulation of Energy Homeostasis

“…Although these effects are in part species specific, acute nicotine administration transiently (5-20 min postinjection) increases locomotion in environments to which a rat has been habituated (Gotti et al, 2010), an effect that undergoes sensitization upon repeated administration (Mao & McGehee, 2010;Vezina, McGehee, & Green, 2007). Nicotine sensitization of habituated locomotion may be due to increased responsiveness to nicotine of the mesolimbic DA neurons (Vezina et al, 2007).…”

Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum

“…The primary nAChRs in CNS dopaminergic systems that mediate the addictive effects of nicotine are the ␣4␤2* and ␣6␤2* subtypes (the asterisk indicates the possible presence of other subunits in the receptor complex) (Barik and Wonnacott, 2009;Changeux, 2010;Mao and McGehee, 2010;De Biasi and Dani, 2011). Evidence for this idea stemmed from studies showing that mice lacking the ␣4, ␣6, and/or ␤2 nAChR subunits fail to self-administer nicotine, whereas re-expression of these subunits in the ventral tegmental area of knockout mice restored nicotine self-administration (Picciotto et al, 1998;Marubio et al, 2003;Maskos et al, 2005;Pons et al, 2008;Jackson et al, 2009;Gotti et al, 2010).…”