Honors Program


Date of this Version

Spring 3-23-2023

Document Type



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.


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

Copyright Sydney Houser 2023.


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 ChantixTM), 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.