Smoking is the leading cause of preventable death worldwide, with <7 % of smoking cessation attempts being met with success. Nicotine, the main addictive agent in cigarettes, enhances the reinforcing value of other environmental rewards. Under some circumstances, this reward enhancement maintains nicotine consumption. Varenicline (i.e., cessation aid Chantix™) also has reward-enhancement effects via nicotinic acetylcholine receptor agonism (nAChRs) – albeit less robust than nicotine. 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. We used 20 (10M, 10F) Sprague-Dawley rats to assess reward-enhancement within-subjects by examining responding maintained by a 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 h session. To assess cotinine and varenicline interactions, rats received an injection of cotinine (saline, 0.1, 1.0, or 6.0 mg/kg) and of varenicline (saline, 0.1, 0.3, 1.0, or 3.0 mg/kg) before the session. While we replicated prior work identifying reward-enhancement by 0.1, 0.3, and 1.0 mg/kg varenicline, cotinine alone did not produce reward-enhancement nor augment the reward-enhancing effects of varenicline. Future studies may consider examining the reward-enhancing effects of cotinine with other reinforcers or co-administered with other smoking cessation aids such as bupropion.

吸烟是全球可预防死亡的主要原因，成功戒烟的尝试只有不到 7%。尼古丁是香烟中的主要成瘾剂，它增强了其他环境奖励的强化价值。在某些情况下，这种奖励的增强会维持尼古丁的消耗。Varenicline （即戒烟辅助药物 Chantix™）还通过烟碱乙酰胆碱受体激动剂 (nAChR) 具有奖励增强作用，尽管不如尼古丁那么强大。可替宁是尼古丁的主要代谢产物。最近的研究表明，可替宁是一种正变构调节剂(PAM) 和/或 nAChR 的弱激动剂。因此，可替宁可以增强nAChR化合物例如伐尼克兰的行为效应和/或单独发挥一些行为效应。我们使用 20 只（10M、10F）Sprague-Dawley 大鼠来评估受试者体内的奖励增强情况，方法是检查可变比率 2 强化计划中强化视觉刺激所维持的反应。为了评估可替宁的奖励增强作用，大鼠在每 1 小时训练前注射一次可替宁（生理盐水，0.1、0.3、1.0、3.0、6.0 mg/kg）。为了评估可替宁和伐尼克兰的相互作用，大鼠在治疗前注射可替宁（盐水，0.1、1.0 或 6.0 mg/kg）和伐尼克兰（盐水，0.1、0.3、1.0 或 3.0 mg/kg）。虽然我们重复了之前的工作，确定了 0.1、0.3 和 1.0 mg/kg 伐尼克兰的奖励增强作用，但单独使用可替宁既不会产生奖励增强，也不会增强伐尼克兰的奖励增强作用。未来的研究可能会考虑检查可替宁与其他强化剂或与其他戒烟辅助剂（例如安非他酮）联合使用的奖励增强作用。