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The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat

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Abstract

Rationale

Previous work has indicated a potential role for γ-aminobutyric acid-B (GABAB) receptor agonists in treating drug addiction in humans. Specifically, GABAB receptor agonists decreased cocaine, heroin and nicotine self-administration in rats.

Objectives

The purpose of the present studies was to extend previous findings by assessing the effects of additional GABAB receptor agonists on nicotine self-administration and food-maintained responding, under both fixed and progressive ratio schedules in rats.

Methods

Male Wistar rats were exposed to a progressive ratio schedule where various nicotine doses were made available according to a within-subjects Latin Square design. Additional groups of rats were used to test the effects of the GABAB receptor agonists baclofen and CGP44532 on nicotine self-administration (0.01 and 0.03 mg/kg per infusion) and food-reinforced responding on fixed and progressive ratio (CGP44532 only) schedules.

Results

Nicotine maintained stable self-administration under a progressive ratio schedule with a linear dose-response function (r=0.61). Both CGP44532 and (−)baclofen dose-dependently reduced nicotine self-administration on the fixed ratio schedule, and also decreased food-maintained responding at higher doses. Further, CGP44532 decreased breakpoints for nicotine and food at identical doses under the progressive ratio schedule.

Conclusion

The present data demonstrate that administration of GABAB receptor agonists decreased intravenous nicotine self-administration under both fixed and progressive ratio schedules of reinforcement, possibly reflecting reduced rewarding effects of nicotine. Both baclofen and CGP44532 exhibited specificity for nicotine- versus food-maintained responding on the fixed ratio schedules but not on the progressive ratio schedule (CGP44532 tested only), indicating the potential usefulness of GABAB receptor agonists as therapeutics for smoking cessation.

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Acknowledgements

This is publication number 14445-NP from The Scripps Research Institute. The authors would like to thank Mike Arends for editorial assistance, and Robert Lintz and Jessica Chevrette for technical assistance. This study was supported by NIDA grant DA11946, DA/NIMH grant U01 MH69062, Tobacco-Related Disease Research Program Grant 12RT-0231 from the State of California, and a Novartis Research Grant to A.M.

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Authors and Affiliations

  1. Department of Neuropharmacology CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

    Neil E. Paterson & Athina Markou

  2. Nervous System Research, Novartis Biomedical Institutes, 4002, Basel, Switzerland

    Wolfgang Froestl

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  1. Neil E. Paterson
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  2. Wolfgang Froestl
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  3. Athina Markou
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Correspondence to Athina Markou.

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Paterson, N.E., Froestl, W. & Markou, A. The GABAB receptor agonists baclofen and CGP44532 decreased nicotine self-administration in the rat. Psychopharmacology 172, 179–186 (2004). https://doi.org/10.1007/s00213-003-1637-1

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  • DOI: https://doi.org/10.1007/s00213-003-1637-1

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