Chronic treatment with varenicline changes expression of four nAChR binding sites in mice

NEUROPHARMACOLOGY

卷:99

Article

Marks, Michael J.^1,2  O'Neill, Heidi C.¹  Wynalda-Camozzi, Kelly M.⁵  Ortiz, Nick C.¹  Simmons, Emily E.¹  Short, Caitlin A.¹  Butt, Christopher M.⁵  McIntosh, J. Michael^3,4  Grady, Sharon R.¹ 

[1] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[2] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[3] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA

[4] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA

[5] DSM Nutr Prod Biol Sci 4, Boulder, CO USA

关键词: Varenicline;    Nicotine;    Chronic treatment;    Nicotinic receptors;   

DOI  :  10.1016/j.neuropharm.2015.07.019

来源: Elsevier

【 摘 要 】

Introduction: Chronic treatment with nicotine is known to increase the alpha 4 beta 2-nAChR sites in brain, to decrease alpha 6 beta 2-nAChR sites and to have minimal effect on alpha 3 beta 4-and alpha 7-nAChR populations. Varenicline is now used as a smoking cessation treatment, with and without continued smoking or nicotine replacement therapy. Varenicline, like nicotine, upregulates the alpha 4 beta 2-nAChR sites; however, it is not known whether varenidine treatment changes expression of the other nAChR subtypes. Methods: Using a mouse model, chronic treatments (10 days) with varenicline (0.12 mg/kg/h) and/or nicotine (1 mg/kg/hr), alone or in combination, were compared for plasma and brain levels of drugs, tolerance to subsequent acute nicotine and expression of four subtypes of nAChR using autoradiography. Results: The upregulation of alpha 4 beta 2-nAChR sites elicited by chronic varenicline was very similar to that elicited by chronic nicotine. Treatment with both drugs somewhat increased up-regulation, indicating that these doses were not quite at maximum effect. Similar down-regulation was seen for alpha 6 beta 2-nAChR sites. Varenicline significantly increased both alpha 3 beta 4-and alpha 7-nAChR sites while nicotine had less effect on these sites. The drug combination was similar to varenicline alone for alpha 3 beta 4-nAChR sites, while for alpha 7 sites the drug combination was less effective than varenicline alone. Varenicline had small but significant effects on tolerance to acute nicotine. Conclusions: Effects of varenicline in vivo may not be limited to the alpha 4 beta 2*-nAChR subtype. In addition, smoking cessation treatment with varenicline may not allow receptor numbers to be restored to baseline and may, in addition, change expression of other receptor subtypes. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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