Long-term nicotine treatment down-regulates α6β2* nicotinic receptor expression and function in nucleus accumbens
Article first published online: 13 OCT 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 127, Issue 6, pages 762–771, December 2013
How to Cite
J. Neurochem.(2013) 127, 762–771.
- Issue published online: 3 DEC 2013
- Article first published online: 13 OCT 2013
- Accepted manuscript online: 30 AUG 2013 09:48PM EST
- Manuscript Accepted: 28 AUG 2013
- Manuscript Revised: 26 AUG 2013
- Manuscript Received: 14 MAY 2013
- National Institutes of Health. Grant Numbers: NS59910, GM103801, GM48677
- California Tobacco Related Disease Research Program. Grant Number: 17RT-0119
- nicotinic receptors;
- nucleus accumbens;
Long-term nicotine exposure induces alterations in dopamine transmission in nucleus accumbens that sustain the reinforcing effects of smoking. One approach to understand the adaptive changes that arise involves measurement of endogenous dopamine release using voltammetry. We therefore treated rats for 2–3 months with nicotine and examined alterations in nAChR subtype expression and electrically evoked dopamine release in rat nucleus accumbens shell, a region key in addiction. Long-term nicotine treatment selectively decreased stimulated α6β2* nAChR-mediated dopamine release compared with vehicle-treated rats. It also reduced α6β2* nAChRs, suggesting the receptor decline may contribute to the functional loss. This decreased response in release after chronic nicotine treatment was still partially sensitive to the agonist nicotine. Studies with an acetylcholinesterase inhibitor demonstrated that the response was also sensitive to increased endogenous acetylcholine. However, unlike the agonists, nAChR antagonists decreased dopamine release only in vehicle- but not nicotine-treated rats. As antagonists function by blocking the action of acetylcholine, their ineffectiveness suggests that reduced acetylcholine levels partly underlie the dampened α6β2* nAChR-mediated function in nicotine-treated rats. As long-term nicotine modifies dopamine release by decreasing α6β2* nAChRs and their function, these data suggest that interventions that target this subtype may be useful for treating nicotine dependence.
Long-term nicotine treatment decreases dopamine (DA) transmission in the mesolimbic dopaminergic system. Our data suggest this may involve a decrease in α6β2* nicotinic receptor expression and function. These changes may play a key role in nicotine reward and dependence.