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The effects of buprenorphine on fentanyl withdrawal in rats

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Abstract

Rationale

Fentanyl is a potent mu-opioid receptor agonist that is widely used for the treatment of severe chronic pain. Discontinuation of fentanyl administration has been shown to induce a negative emotional state.

Objectives

The aim of the present studies was to investigate the effects of the partial mu-opioid receptor agonist buprenorphine on the negative emotional state associated with precipitated and spontaneous fentanyl withdrawal in rats.

Materials and methods

Fentanyl and saline were chronically administered via osmotic minipumps. A discrete-trial intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs.

Results

Naloxone induced a deficit in brain reward function in rats chronically treated with fentanyl. Buprenorphine dose-dependently prevented the naloxone-induced deficit in brain reward function. Discontinuation of fentanyl administration was also associated with a deficit in brain reward function. After explantation of the minipumps, the administration of buprenorphine induced a potentiation of brain reward function in the fentanyl-withdrawing rats, but did not affect brain reward function of saline-treated control rats. Buprenorphine prevented the somatic withdrawal signs associated with spontaneous fentanyl withdrawal and attenuated the somatic signs associated with precipitated fentanyl withdrawal.

Conclusions

Buprenorphine prevents affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is rewarding in rats previously exposed to fentanyl, but not in opioid-naïve rats. This pattern of results suggests that buprenorphine may be an effective treatment for the anhedonic-state associated with fentanyl withdrawal, but further study of buprenorphine’s abuse potential is warranted.

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Acknowledgements

This work was funded by developmental funds from the Department of Psychiatry (University of Florida) and a National Institute on Drug Abuse grant (RO3 DA020502-01) to Adrie Bruijnzeel. The authors would like to thank Melissa Prado and George Zislis for excellent technical assistance.

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Authors and Affiliations

  1. Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, 100 S. Newell Dr., 100256, Gainesville, FL, 32610-0244, USA

    Adrie W. Bruijnzeel, Catherine Marcinkiewcz, Shani Isaac & Mark S. Gold

  2. Department of Anesthesiology, College of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610-0254, USA

    Matthew M. Booth, Donn M. Dennis & Mark S. Gold

  3. Department of Pharmacology and Experimental Therapeutics, College of Medicine, University of Florida, P.O Box 100254, Gainesville, FL, 32610-0254, USA

    Donn M. Dennis

  4. Department of Neuroscience, College of Medicine, University of Florida, 100 S. Newell Dr., Gainesville, FL, 32610-0244, USA

    Mark S. Gold

  5. Department of Community Health and Family Medicine, College of Medicine, University of Florida, 100 S. Newell Dr., Gainesville, FL, 32610-0244, USA

    Mark S. Gold

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  1. Adrie W. Bruijnzeel
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  2. Catherine Marcinkiewcz
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  3. Shani Isaac
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  4. Matthew M. Booth
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  6. Mark S. Gold
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Correspondence to Adrie W. Bruijnzeel.

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Bruijnzeel, A.W., Marcinkiewcz, C., Isaac, S. et al. The effects of buprenorphine on fentanyl withdrawal in rats. Psychopharmacology 191, 931–941 (2007). https://doi.org/10.1007/s00213-006-0670-2

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