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The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat

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Abstract

Rationale

Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence.

Objectives

The aim of this work was to evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats.

Materials and methods

A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic mini pumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via mini pump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing mini pumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure.

Results

Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding.

Conclusions

The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal and may alter the rewarding effects of nicotine and food.

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Acknowledgments

The authors would like to thank Mr. Michael Arends for editorial assistance and Mrs. Jessica Benedict and Mr. Randy Ares for technical assistance. The authors would also like to thank Dr. John F. Cryan for initial work with the effects of acute desipramine during amphetamine withdrawal in our laboratory. NEP was supported by Post-Doctoral Fellowship 14-FT0056 from the Tobacco Related Disease Research Program (State of California) and a research grant from The Peter F. McManus Charitable Trust. This work was supported by National Institute of Mental Health grants R01 MH62527 and U01 MH69062 to AM. The authors report no actual or potential financial conflicts of interest.

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  1. Neil E. Paterson

    Present address: Department of Psychiatry, Semel Institute for Neuroscience & Human Behavior, University of California at Los Angeles, Los Angeles, CA, 90095-1563, USA

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  1. Department of Psychiatry, 0603 School of Medicine, University of California at San Diego, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA

    Svetlana Semenova & Athina Markou

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  1. Neil E. Paterson
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Correspondence to Athina Markou.

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Paterson and Semenova contributed equally to this work.

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Paterson, N.E., Semenova, S. & Markou, A. The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat. Psychopharmacology 198, 351–362 (2008). https://doi.org/10.1007/s00213-008-1144-5

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