Alpha7-nicotinic receptors modulate nicotine-induced reinforcement and extracellular dopamine outflow in the mesolimbic system in mice

作者：Besson Morgane^*; David Vincent; Baudonnat Mathieu; Cazala Pierre; Guilloux Jean Philippe; Reperant Christelle; Cloez Tayarani Isabelle; Changeux Jean Pierre; Gardier Alain M; Granon Sylvie

来源：Psychopharmacology, 2012, 220(1): 1-14.

DOI：10.1007/s00213-011-2422-1

• Nicotine
• Nicotinic receptors
• Knockout mice
• Ventral tegmental area
• Nucleus accumbens
• Reinforcement
• Dopamine

Rationale Nicotine is the main addictive component of tobacco and modifies brain function via its action on neuronal acetylcholine nicotinic receptors (nAChRs). The mesolimbic dopamine (DA) system, where neurons of the ventral tegmental area (VTA) project to the nucleus accumbens (ACb), is considered a core site for the processing of nicotine's reinforcing properties. However, the precise subtypes of nAChRs that mediate the rewarding properties of nicotine and that contribute to the development of addiction remain to be identified.
Objectives We investigated the role of the nAChRs containing the alpha 7 nicotinic subunit (alpha 7*nAChRs) in the reinforcing properties of nicotine within the VTA and in the nicotine-induced changes in ACb DA outflow in vivo.
Methods We performed intra-VTA self-administration and microdialysis experiments in genetically modified mice lacking the alpha 7 nicotinic subunit or after pharmacological blockade of alpha 7*nAChRs in wild-type mice.
Results We show that the reinforcing properties of nicotine within the VTA are lower in the absence or after pharmacological blockade of alpha 7* nAChRs. We also report that nicotine-induced increases in ACb DA extracellular levels last longer in the absence of these receptors, suggesting that alpha 7* nAChRs regulate the action of nicotine on DA levels over time.
Conclusions The present results reveal new insights for the role of alpha 7* nAChRs inmodulating the action of nicotine within the mesolimbic circuit. These receptors appear to potentiate the reinforcing action of nicotine administered into the VTA while regulating its action over time on DA outflow in the ACb.

• 出版日期2012-3