Contextual stimuli modulate extinction and reinstatement in rodents self-administering intravenous nicotine

Abstract

Discrete cues, such as drug-associated paraphernalia, play an important role in tobacco smoking and relapse, an effect that can be modelled in the nicotine-seeking behaviour of laboratory animals. However, the role of contextual stimuli (i.e. the drug taking environment) within nicotine dependence is less clear. The present study investigated the effects of contextual stimuli on nicotine detoxification and relapse. Male hooded Lister rats were trained to self-administer nicotine (0.03 mg/kg/infusion) in one of two distinct environmental contexts: transparent walls and rod floor or checkerboard walls and grid floor. Extinction of drug-seeking behaviour, either in the acquisition context or alternate context, was achieved by removing both nicotine infusions and response-contingent cues. The two contexts were then presented with or without nicotine priming and response-contingent cue presentation. The initial rate of extinction was quicker in a novel environment compared to in the same context as training, although similar low levels of responding were eventually reached. Nicotine priming and re-presentation of cues resulted in significant reinstatement of nicotine-seeking behaviour, but there was a trend towards a reduction in this effect when conducted in a novel environment. In addition, re-presentation of the acquisition context after extinction in the alternate context produced a significant reinstatement of nicotine-seeking behaviour without the need for nicotine priming and re-presentation of cues. Contextual stimuli are capable of modulating the extinction and reinstatement of nicotine-seeking behaviour, and exposure to environments previously associated with smoking may lead to an increased risk of relapse. Context is an additional factor that could be targeted when developing smoking cessation strategies. For example, the long-term success of cue exposure might be improved by conducting treatment in multiple settings.