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Cue-induced reinstatement of nicotine-seeking behavior in rats: effect of bupropion, persistence over repeated tests, and its dependence on training dose

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Abstract

Rationale

The motivational effects of nicotine-associated cues have been demonstrated in animal studies. However, it is unknown whether the effectiveness of nicotine cues in reinstating nicotine-seeking varies with the extent of prior nicotine self-administration. In addition, the issue of whether bupropion (an FDA-approved smoking cessation medication) interferes with the conditioned incentive of nicotine cues remains to be addressed.

Objective

This study determined the relationship of cue-reinstated nicotine-seeking and the levels of prior self-administration and examined the effect of bupropion on cue-induced reinstatement of nicotine-seeking in comparison with that on self-administration.

Materials and methods

Male Sprague–Dawley rats were trained in daily 1-h sessions to intravenously self-administer nicotine at different doses (0, 0.015, 0.03, 0.06 mg/kg/infusion) and to associate an auditory/visual cue with each nicotine delivery. After extinction, three reinstatement tests at 15 day intervals were conducted with re-presentation of the cue without nicotine delivery. In separate groups of rats trained with 0.03 mg/kg/infusion nicotine, bupropion (0, 10, 20, 40 mg/kg) was intraperitoneally administered to different groups before the reinstatement and in a within-subject design before the self-administration tests.

Results

Cue-induced reinstatement of active lever responses was observed at all nicotine doses in the first reinstatement test, but at only the two highest doses during the second and third tests. The magnitude of reinstatement was positively correlated with level of prior responding for nicotine. Bupropion pretreatment decreased nicotine self-administration but enhanced cue-reinstated nicotine-seeking.

Conclusions

These results demonstrate the positive correlation of cue-reinstated nicotine-seeking with prior responding for nicotine self-administration and the persistence of the cue effect after taking higher doses of nicotine. The results of pharmacological tests suggest that although it is able to help achieve smoking cessation, bupropion may have little clinical benefit for the prevention of relapse associated with exposure to environmental smoking cues.

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Acknowledgements

This work was supported by NIH grant DA 17288 (X Liu) and DA 10464 (AR Caggiula) from the National Institute on Drug Abuse. The authors would like to thank Sheri Booth, Maysa Gharib, Laure Craven, and Nicole Roehrig for their technical assistance.

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  1. Department of Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Xiu Liu, Anthony R. Caggiula, Matthew I. Palmatier & Eric C. Donny

  2. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Alan F. Sved

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  1. Xiu Liu
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  2. Anthony R. Caggiula
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Correspondence to Xiu Liu.

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Liu, X., Caggiula, A.R., Palmatier, M.I. et al. Cue-induced reinstatement of nicotine-seeking behavior in rats: effect of bupropion, persistence over repeated tests, and its dependence on training dose. Psychopharmacology 196, 365–375 (2008). https://doi.org/10.1007/s00213-007-0967-9

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