Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self-administration

Nicotine produces robust stimulus effects that can be conditioned to exert stimulus control over behavior through associative learning. Additionally, nicotine has weak reinforcing effects that are inconsistent with its prevalence of use and the tenacity of nicotine dependence. The present study investigated whether conditioned associations to the nicotine drug stimulus may confer additional reinforcing strength to nicotine that thereby increase its use liability, and presents a new methodological approach to investigating the interaction between the stimulus effects and reinforcing effects of drugs. Male and female Sprague-Dawley rats were divided into groups receiving intravenous infusions of either 0.03 mg/kg nicotine or 0.9% saline that were either Paired (30 s delayed) or explicitly Unpaired (4 to 6 min delayed) with sucrose deliveries over 24 daily conditioning sessions. Thereafter, recessed nosepoke response devices were installed in the chambers and infusions of their assigned drug solutions were contingently available according to a progressive ratio schedule. Rats in the Paired Nicotine condition acquired the nosepoke response, expressed active nosepoke discrimination, and self-administered significantly more infusions than rats in any of the other groups. These results demonstrate that the interoceptive stimulus effects of nicotine can form Pavlovian associations with reinforcing events that alter its reinforcement efficacy.