Measurement of affective state during chronic nicotine treatment and withdrawal by affective taste reactivity in mice: The role of endocannabinoids

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 33A c c e p t e d M a n u s c r i p t This work was funded by the RIKEN Brain Science Institute, and a BBSRC Japan Partnering Award. Page 2 of 33A c c e p t e d M a n u s c r i p t 2 AbstractDespite tobacco being highly addictive, it is unclear if nicotine has significant affective properties. To address this, we studied taste reactions to gustatory stimuli, palatable sucrose and unpalatable quinine, which are believed to reflect ongoing affective state. Taste reactivity was assessed during chronic nicotine administration and spontaneous withdrawal and the role of the endogenous cannabinoids was also investigated. C57BL6J mice were implanted with intra-oral fistula to allow passive administration of solutions. In the first study, taste reactivity was tracked throughout chronic vehicle or nicotine (12 mg/kg/day) infusion via osmotic minipumps and spontaneous withdrawal following removal of minipumps. In the second study, the endocannabinoid CB1 receptor antagonist AM251 (1, 3 and 10 mg/kg, intraperitoneal) or vehicle were acutely administered before taste reactivity measurement during chronic nicotine administration. Chronic nicotine treatment and spontaneous withdrawal did not influence taste reactions to sucrose or quinine. AM251 decreased positive reactions to sucrose and increased negative reactions to quinine. The effects of AM251 were respectively attenuated and enhanced in nicotine infused mice. These results suggest chronic nicotine exposure and withdrawal has no apparent affective sequelae, as probed by taste reactivity, and thus may not explain the difficulty tobacco-users have in achieving abstinence. In contrast, endocannabinoids elevates affective state in drug-naïve animals and changes in endogenous endocannabinoid tone may underlie compensations in affective state during chronic nicotine exposure.

Mouse models for studying genetic influences on factors determining smoking cessation success in humans

“…Other approaches that can be taken to assess affective differences, either premorbid differences or those that occur during withdrawal, include measurement of oral‐facial responses to palatable (sucrose) and unpalatable substances (quinine). However, neither chronic nicotine administration nor withdrawal alters affective state using these behavioral outcomes 327 . As mentioned in previous sections, chronic nicotine administration produced elevations in brain stimulation–reward thresholds (anhedonia) as well as increased anxiety upon either spontaneous or precipitated nicotine withdrawal in C57BL/6J and BALB/cByJ mice 127,140 .…”