Abstract
Rationale
Nicotine intravenous self-administration (IVSA) in rats has been conducted using a variety of methodological procedures with equally variable results.
Objectives
Here, we addressed the importance of the type of response operandum and prior instrumental training with a natural reinforcer on nicotine IVSA and reinstatement.
Methods
Rats were tested for spontaneous acquisition of IVSA using either nose poke (NP) or lever press (LVR) operandum. A dose-response test was then conducted, followed by extinction and cue- and nicotine-induced reinstatement.
Results
The use of the NP operandum resulted in markedly higher levels of IVSA across acquisition and across dose-response testing compared with the LVR group. Whereas both groups reinstated following a nicotine prime, only the LVR group demonstrated cue-induced reinstatement. As a positive control, the experiment was repeated with cocaine as the reinforcer: equivalent levels of IVSA were observed across all tests, irrespective of operandum. When rats self-administering nicotine received instrumental training with a sucrose reinforcer prior to IVSA, a facilitated acquisition of IVSA was observed in both LVR and NP groups to a similar extent (the effect of operandum remained), but had little effect on responding thereafter. During reinstatement testing, both groups now displayed cue- and nicotine-induced reinstatement, but this was also evident in saline control animals that had never received nicotine.
Conclusions
These results suggest that, unlike cocaine, an increased physical response requirement can decrease nicotine intake. It also indicates that operandum and prior sucrose training may influence the role that visual cues play in nicotine dependence.
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Acknowledgments
The authors are solely responsible for the scientific content of this paper. This research and KJC were supported by funding from the Association pour la Recherche sur les Nicotianées (ARN), Centre National de la Recherche Scientifique, Universities Bordeaux 1 and 2 and Region Aquitaine, France. The authors would also like to thank Anne Fayoux and Stephane Lelgouach for animal care, Marie-Hélène Bruyères for administrative assistance and Dr. Nathan Holmes for comments on the manuscript.
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The authors have no known conflict of interest.
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This research and KJC were supported by funding from the Association pour la Recherche sur les Nicotianées (ARN), France.
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Supplementary Fig. 1
Extinction of responding in rats previously lever pressing (LVR) or nose-poking (NP) for A) nicotine, B) cocaine, C) saline, D) nicotine in rats previously trained with sucrose and E) saline in rats previously trained with sucrose. The first data point (FR-5) represents the mean responding across the last 3 days of responding on a FR-5 schedule. n = 4-10 rats per group. (GIF 86.2 kb)
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Clemens, K.J., Caillé, S. & Cador, M. The effects of response operandum and prior food training on intravenous nicotine self-administration in rats. Psychopharmacology 211, 43–54 (2010). https://doi.org/10.1007/s00213-010-1866-z
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DOI: https://doi.org/10.1007/s00213-010-1866-z