Exploring the Reward-Enhancing Effects of Continine and Its Interactions with Varenicline in Sprague-Dawley Rats

Authors

Sydney Houser, University of Nebraska - LincolnFollow

Date of this Version

Spring 3-23-2023

Document Type

Thesis

Citation

Houser, S.D., McNealy, K.R., Barrett, S.T., & Bevins, R.A. (IN PREP). 2023. Exploring the Reward-Enhancing Effects of Continine and Its Interactions with Varenicline in Sprague-Dawley Rats. Undergraduate Honors Thesis. University of Nebraska - Lincoln.

Comments

Likely will be submitting to Pharmacology Brain and Behavior or Behavioral Brain Research.

Copyright Sydney Houser 2023.

Abstract

Smoking is the leading cause of preventable death worldwide. Despite this, less than 7% of smoking cessation attempts are successful. Nicotine, the main addictive agent in cigarettes, enhances the value of environmental stimuli and rewards. This reward-enhancement maintains nicotine consumption. Varenicline (cessation aid Chantix^TM), produces similar, but lesser, reward-enhancement effects compared to nicotine via nicotinic acetylcholine receptors (nAChRs). Cotinine is the major metabolite of nicotine. Recent studies suggest that cotinine is a positive allosteric modulator (PAM) and/or a weak agonist at nAChRs. Thus, cotinine may enhance the behavioral effects of nAChR compounds such as varenicline and/or exert some behavioral effects alone. To date, no study has examined cotinine’s reward-enhancing effects alone nor co-administered with varenicline. This study sought to determine whether cotinine would produce reward-enhancing effects alone or alter the reward-enhancing effects of varenicline. We used 20 (10M, 10F) Sprague-Dawley rats to assess reward-enhancement within-subjects by examining responding maintained by a weakly reinforcing visual stimulus on a Variable Ratio 2 schedule of reinforcement. To assess the reward-enhancing effects of cotinine, rats received one injection of cotinine (saline, 0.1, 0.3, 1.0, 3.0, 6.0 mg/kg) before each 1 hr session. To assess the reward-enhancing effects of co-administered cotinine and varenicline, rats received an injection of cotinine (saline, 0.1, 1.0, 6.0 mg/kg) and one of varenicline (saline, 0.1, 0.3, 1.0, 3.0 mg/kg). Cotinine alone did not enhance the reinforcing efficacy of a visual stimulus. We replicated prior work identifying reward-enhancement by 0.1, 0.3, and 1.0 mg/kg varenicline. However, cotinine did not augment the reward-enhancing effects of varenicline.