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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2019.00159

Varenicline targets the reinforcing-enhancing effect of nicotine on its associated salient cue during nicotine self-administration in the rat

 Véronique DEROCHE-GAMONET1*,  Vernon Garcia-Rivas1, Jean-Francois Fiancette1,  Nazzareno Cannella1, Maria Carbo-Gas1, Prisca Renault1 and Jessica Tostain1
  • 1INSERM U1215 Neurocentre Magendie, France

Nicotine is acknowledged as the key addictive compound of tobacco. Varenicline (Champix® or Chantix®), mainly acting as a partial agonist at the α4β2 nicotinic receptor, is an approved smoking cessation pharmacotherapy, although with efficacy limited to a portion of smokers. Smokers differ in the motives that drive their drug seeking and Varenicline might be more efficient in some groups more than others. Studies in rodents revealed that nicotine seeking is strongly supported by complex interactions between nicotine and environmental cues, and notably the ability of nicotine to enhance the reinforcing properties of salient environmental stimuli. It is not yet understood whether the decrease of nicotine seeking by acute Varenicline in rats results from antagonism of the primary reinforcing effects of nicotine, of the reinforcement-enhancing effect of nicotine on cues, or of a combination of both.
Thanks to a protocol that allows assessment of the reinforcement-enhancing effect of nicotine on cues during self-administration in rats, we showed that Varenicline targets both nicotine reinforcing effects and reinforcement-enhancing effect of nicotine on cues, but importantly, individual variations in the latter, and not in the former, determined the amplitude of acute Varenicline-induced decrease in seeking.
These results suggest that Varenicline might be more beneficial in smokers who are more sensitive to nicotine effects on surrounding stimuli, and less for those who seek nicotine primarily for its primary reinforcing effects.

Keywords: intravenous self-administration, Nicotine, Cues, individual differences, varenicline, rat

Received: 25 Apr 2019; Accepted: 01 Jul 2019.

Edited by:

Rutsuko Ito, University of Toronto, Canada

Reviewed by:

Kelly J. Clemens, University of New South Wales, Australia
Anh D. Le, Centre for Addiction and Mental Health (CAMH), Canada  

Copyright: © 2019 DEROCHE-GAMONET, Garcia-Rivas, Fiancette, Cannella, Carbo-Gas, Renault and Tostain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Véronique DEROCHE-GAMONET, INSERM U1215 Neurocentre Magendie, Bordeaux, 33000, Aquitaine, France, veronique.deroche@inserm.fr