Abstract
Cue reinstatement of extinguished cocaine-seeking behavior is a widely used model of cue-elicited craving in abstinent human addicts. This study examined Fos protein expression in response to cocaine cues or to novel cues as a control for activation produced by test novelty. Rats were trained to self-administer cocaine paired with either a light or a tone cue, or received yoked saline and cue presentations, and then underwent daily extinction training. They were then tested for reinstatement of extinguished cocaine-seeking behavior elicited by response-contingent presentations of either the cocaine-paired cue or a novel cue (that is, tone for those trained with a light or vice versa). Surprisingly, conditioned and novel cues both reinstated responding and increased Fos similarly in most brain regions. Exceptions included the anterior cingulate, which was sensitive to test cue modality in saline controls and the dorsomedial caudate-putamen, where Fos was correlated with responding in the novel, but not conditioned, cue groups. In subsequent experiments, we observed a similar pattern of reinstatement in rats trained and tested for sucrose-seeking behavior, whereas rats trained and tested with the cues only reinstated to a novel, and not a familiar, light or tone. The results suggest that novel cues reinstate responding to a similar extent as conditioned cues regardless of whether animals have a reinforcement history with cocaine or sucrose, and that both types of cues activate similar brain circuits. Several explanations as to why converging processes may drive drug and novel cue reinforcement and seeking behavior are discussed.
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Acknowledgements
This work was supported by NIDA grants DA11064 and DA 021485. We thank Timothy Cheung, Natalie Peartree, Lara Pockros, Tom Shepherd, Krista Heintzelman, Claudia Vargas, Lauren Hood, Stephanie Kost, and Katie Olsen for technical contributions and Dr Joshua Talboom for his advice with statistics.
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JN has received honoraria for seminar presentations given at the conference of the Association for Behavioral Analysis International, the University of Texas Health Sciences Center at San Antonio, Oregon Health and Sciences University, University of North Carolina-Chapel Hill, and Florida State University. The authors declare no conflict of interest.
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Bastle, R., Kufahl, P., Turk, M. et al. Novel Cues Reinstate Cocaine-Seeking Behavior and Induce Fos Protein Expression as Effectively as Conditioned Cues. Neuropsychopharmacol 37, 2109–2120 (2012). https://doi.org/10.1038/npp.2012.60
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DOI: https://doi.org/10.1038/npp.2012.60
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