Interoceptive conditioning with nicotine using extinction and re-extinction to assess stimulus similarity with bupropion

Abstract

Bupropion is an atypical antidepressant that increases long-term quit rates of tobacco smokers. A better understanding of the relation between nicotine and this first-line medication may provide insight into improving treatment. For all experiments, rats first had nicotine (0.4 mg base/kg) and saline session intermixed; intermittent access to sucrose only occurred on nicotine session. Nicotine in this protocol comes to differentially control “anticipatory” dipper entries. To more closely examine the overlap in the interoceptive stimulus effects of nicotine and bupropion, we assessed whether subsequent prolonged and repeated non-reinforced (extinction) sessions with the bupropion stimulus could weaken responding to nicotine (i.e., transfer of extinction). We also examined whether retraining the discrimination after initial extinction and then conducting extinction again (i.e., re-extinction) with bupropion would affect responding. We found that bupropion (20 and 30 mg/kg) fully substituted for the nicotine stimulus in repeated 20-min extinction sessions. The extent of substitution in extinction did not necessarily predict performance in the transfer test (e.g., nicotine responding unchanged after extinction with 20 mg/kg bupropion). Generalization of extinction back to nicotine was not seen with 20 mg/kg bupropion even after increasing the number of extinction session from 6 to 24. Finally, there was evidence that learning in the initial extinction phase was retained in the re-extinction phase for nicotine and bupropion. These findings indicate that learning involving the nicotine stimuli are complex and that assessment approach for stimulus similarity changes conclusions regarding substitution by bupropion. Further research will be needed to identify whether such differences may be related to different facets of nicotine dependence and/or its treatment.

The effect of switching pharmacological intervention during extinction on nicotine-evoked conditioned responding in rats

“…One such factor, and our focus in this report, is learning which involves the interoceptive nicotine stimulus and its contribution to the tenacity of the smoking habit and nicotine dependence (Besheer et al , 2004; Bevins et al , 2012; Bevins and Murray, 2011; Charntikov et al , 2014; Glautier et al , 1996; Polewan et al , 2013; Troisi, 2006). To determine the role of learned associations with the nicotine stimulus, our lab utilizes a discriminated goal-tracking task (Besheer et al , 2004; Charntikov et al , 2014; Pittenger and Bevins, 2013a; Polewan et al , 2013).…”

“…To determine the role of learned associations with the nicotine stimulus, our lab utilizes a discriminated goal-tracking task (Besheer et al , 2004; Charntikov et al , 2014; Pittenger and Bevins, 2013a; Polewan et al , 2013). In this task, rats are administered nicotine prior to conditioning sessions in which there is intermittent access to sucrose.…”

“…Appetitive behavior controlled by nicotine is also sensitive to reinforcer devaluation (Pittenger and Bevins, 2013b) and extinction (Besheer et al , 2004; Charntikov et al , 2014; Murray et al , 2009b; Pittenger et al , 2013a; Polewan et al , 2013; Wilkinson et al , 2006). Extinction refers to the non-reinforced presentations of the nicotine stimulus that was previously paired with a reinforcer.…”

“…Extinction refers to the non-reinforced presentations of the nicotine stimulus that was previously paired with a reinforcer. Removal of the reinforcer produces a progressive decrease in conditioned responding evoked by the nicotine stimulus (Besheer et al , 2004; Charntikov et al , 2014; Murray and Bevins, 2007, 2009a; Polewan et al , 2013; Wilkinson et al , 2006). …”

“…Of interest here is the related finding that responding evoked by nicotine can be weakened when extinction is conducted with a compound that shares stimulus elements with nicotine (Bevins et al , 2012; Charntikov et al , 2014; Reichel et al , 2010). In one study, Reichel et al (2010) first trained rats in the nicotine discriminated goal-tracking task as described earlier.…”