Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal

An important factor contributing to the high relapse rates among smokers is nicotine withdrawal symptoms. Multiple studies suggest that decreased dopamine release in nucleus accumbens plays a key role in withdrawal. However, recent reports showed that long-term nicotine exposure itself also decrease...

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Main Authors:	Perez, Xiomara A, Khroyan, Taline V, McIntosh, J Michael, Quik, Maryka
Format:	Online
Language:	English
Published:	BlackWell Publishing Ltd 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317236/

id	pubmed-4317236
recordtype	oai_dc
spelling	pubmed-43172362015-02-17 Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal Perez, Xiomara A Khroyan, Taline V McIntosh, J Michael Quik, Maryka Original Articles An important factor contributing to the high relapse rates among smokers is nicotine withdrawal symptoms. Multiple studies suggest that decreased dopamine release in nucleus accumbens plays a key role in withdrawal. However, recent reports showed that long-term nicotine exposure itself also decreases accumbal dopamine release, suggesting that additional mechanisms are involved in withdrawal. Here, we used real-time cyclic voltammetry in brain slices containing the nucleus accumbens to further elucidate the changes in dopamine release linked to nicotine withdrawal. Rats received vehicle or nicotine via the drinking water for 2–3 months. Studies assessing the expression of somatic signs in vehicle-treated, nicotine-treated, and 24-h nicotine withdrawn rats showed that nicotine withdrawal led to a significant increase in somatic signs. Subsequent voltammetry studies showed that long-term nicotine decreased single-pulse-stimulated dopamine release via an interaction at α6β2* receptors. Nicotine withdrawal led to a partial recovery in α6β2* receptor-mediated release. In addition, long-term nicotine treatment alone increased dopamine release paired-pulse ratios and this was partially reversed with nicotine removal. We then evaluated the effect of bath-applied nicotine and varenicline on dopamine release. Nicotine and varenicline both decreased single-pulse-stimulated release in vehicle-treated, nicotine-treated, and nicotine withdrawn rats. However, bath-applied varenicline increased paired-pulse ratios to a greater extent than nicotine during long-term nicotine treatment and after its withdrawal. Altogether these data suggest that nicotine withdrawal is associated with a partial restoration of dopamine release measures to control levels and that varenicline's differential modulation of dopamine release may contribute to its mechanism of action. BlackWell Publishing Ltd 2015-02 2014-12-16 /pmc/articles/PMC4317236/ /pubmed/25692023 http://dx.doi.org/10.1002/prp2.105 Text en © 2015 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Perez, Xiomara A Khroyan, Taline V McIntosh, J Michael Quik, Maryka
spellingShingle	Perez, Xiomara A Khroyan, Taline V McIntosh, J Michael Quik, Maryka Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
author_facet	Perez, Xiomara A Khroyan, Taline V McIntosh, J Michael Quik, Maryka
author_sort	Perez, Xiomara A
title	Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
title_short	Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
title_full	Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
title_fullStr	Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
title_full_unstemmed	Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
title_sort	varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal
description	An important factor contributing to the high relapse rates among smokers is nicotine withdrawal symptoms. Multiple studies suggest that decreased dopamine release in nucleus accumbens plays a key role in withdrawal. However, recent reports showed that long-term nicotine exposure itself also decreases accumbal dopamine release, suggesting that additional mechanisms are involved in withdrawal. Here, we used real-time cyclic voltammetry in brain slices containing the nucleus accumbens to further elucidate the changes in dopamine release linked to nicotine withdrawal. Rats received vehicle or nicotine via the drinking water for 2–3 months. Studies assessing the expression of somatic signs in vehicle-treated, nicotine-treated, and 24-h nicotine withdrawn rats showed that nicotine withdrawal led to a significant increase in somatic signs. Subsequent voltammetry studies showed that long-term nicotine decreased single-pulse-stimulated dopamine release via an interaction at α6β2* receptors. Nicotine withdrawal led to a partial recovery in α6β2* receptor-mediated release. In addition, long-term nicotine treatment alone increased dopamine release paired-pulse ratios and this was partially reversed with nicotine removal. We then evaluated the effect of bath-applied nicotine and varenicline on dopamine release. Nicotine and varenicline both decreased single-pulse-stimulated release in vehicle-treated, nicotine-treated, and nicotine withdrawn rats. However, bath-applied varenicline increased paired-pulse ratios to a greater extent than nicotine during long-term nicotine treatment and after its withdrawal. Altogether these data suggest that nicotine withdrawal is associated with a partial restoration of dopamine release measures to control levels and that varenicline's differential modulation of dopamine release may contribute to its mechanism of action.
publisher	BlackWell Publishing Ltd
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317236/
_version_	1613184292678008832

Varenicline enhances dopamine release facilitation more than nicotine after long-term nicotine treatment and withdrawal

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