Interoceptive conditioning with the nicotine stimulus

Abstract

Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

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

“…All injections were subcutaneous (SC) in a volume of 1 ml/kg. Previous research suggests the doses utilized in this study and reported below produce robust discrimination and optimal transfer of extinction back to nicotine (Besheer et al , 2004; Polewan et al , 2013; Reichel et al , 2010). …”

“…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). …”