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Role of nicotinic acetylcholine receptors in the effects of cocaine-paired contextual stimuli on impulsive decision making in rats

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Abstract

Rationale

Chronic cocaine exposure produces unconditioned enhancement in impulsive decision making; however, little is known about the effects of cocaine-paired conditioned stimuli on this behavior. Thus, this study explored the effects of cocaine-paired contextual stimuli on impulsive decision making and the contribution of nicotinic acetylcholine receptors (nAChRs) to this phenomenon.

Methods

Rats were trained to achieve stable performance on a delay discounting task, which involved lever press-based choice between a single food pellet (small reward) available immediately and three food pellets (large reward) available after a 10-, 20-, 40-, or 60-s time delay. Rats then received Pavlovian context-cocaine (15 mg/kg, i.p.) and context-saline (1 ml/kg, i.p.) pairings in two other, distinct contexts. Subsequently, delay discounting task performance was assessed in the previously cocaine-paired or saline-paired context following pretreatment with saline or cocaine (15 mg/kg, Experiment 1) or with saline or the nAChR antagonist, mecamylamine (0.2 and 2 mg/kg, Experiment 2), using counterbalanced within-subjects testing designs.

Results

Independent of cocaine pretreatment, rats exhibited greater decrease in preference for the large reward as a function of delay duration in the cocaine-paired context, relative to the saline-paired context. Furthermore, systemic mecamylamine pretreatment dose-dependently attenuated the decrease in preference for the large reward in the cocaine-paired context, but not in the saline-paired context, as compared to saline.

Conclusion

Cocaine-paired contextual stimuli evoke a state of impulsive decision making, which requires nAChR stimulation. Drug context-induced impulsivity likely increases the propensity for drug relapse in cocaine users, making the nAChR an interesting target for drug relapse prevention.

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Acknowledgements

The authors thank Antonia Bista, Christopher Hanlin, and Dr. Heather Lasseter for excellent technical assistance and insightful comments on an earlier version of this manuscript. The authors declare no conflict interest. This work was supported by the National Institute on Drug Abuse grants DA017673 and DA025646.

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Correspondence to Rita A. Fuchs.

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Xie, X., Arguello, A.A., Reittinger, A.M. et al. Role of nicotinic acetylcholine receptors in the effects of cocaine-paired contextual stimuli on impulsive decision making in rats. Psychopharmacology 223, 271–279 (2012). https://doi.org/10.1007/s00213-012-2715-z

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  • DOI: https://doi.org/10.1007/s00213-012-2715-z

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