Cigarette smoke extract and nicotine evoke similar interoceptive effects in a Pavlovian occasion setting task in male and female Sprague-Dawley rats

Introduction Although nicotine is the primary component of interest in tobacco, the other ~9500 constituents in tobacco are thought to interact with nicotine to contribute to the pharmacological effects relevant to tobacco use disorder. These other tobacco constituents may also contribute to providing an interoceptive stimulus unique from that of nicotine alone. Using a Pavlovian drug discrimination task, we assessed whether rats could discriminate between nicotine and cigarette smoke extract (CSE) of the same nicotine concentration (0.2 mg/kg) based on the presence of constituent chemicals. Methods: Rats were assigned to one of three training conditions in which intermixed daily injections were administered before chamber placement. The interoceptive stimulus elicited by the injected compound would set the occasion on which a light conditioned stimulus (CS) would, or would not, be followed by sucrose. Increased dipper entries during the CS indicate greater anticipation of impending sucrose. Groups included 1) nicotine vs vehicle with nicotine signaling sucrose, 2) CSE vs vehicle with CSE signaling sucrose, and 3) CSE vs nicotine with CSE signaling sucrose. This final group determined whether rats could discriminate based on other tobacco constituents. Results: Subjects readily discriminated between nicotine and vehicle and between CSE and vehicle within ~20 training sessions; however, they were unable to discriminate between CSE and nicotine after 72 sessions. Conclusions: Our results confirm that CSE is a successful Pavlovian discriminative stimulus and adds to previous nicotine literature. Interestingly, we demonstrate that CSE and nicotine do not create distinct interoceptive environments under current training conditions. Implications Nicotine has long been used as a proxy for tobacco in non-human animal studies. However, there has always been an undercurrent regarding the appropriateness of this approach given the myriad constituents in tobacco. Though generalization to other behavioural preparations must be done with extreme caution, the current findings suggest that, at least in some capacity, there is overlap in the stimulus characteristics of nicotine and CSE.