Long-term effects of chronic nicotine exposure on brain nicotinic receptors.

M. Besson, S. Granon, M. Mameli-Engvall, I. Cloez-Tayarani, N. Maubourguet, A. Cormier, P. Cazala, V. David, J.-P. Changeux, P. Faure
Proceedings of the National Academy of Sciences. 2007-04-30; 104(19): 8155-8160
DOI: 10.1073/pnas.0702698104

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Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide  behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by  beta2*- vs. alpha7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on beta2*- or alpha7*nAChRs.


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