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Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine

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Abstract

Objective

Previous studies demonstrated that the dynorphin/κ opioid system was up-regulated upon repeated cocaine self-administration. In the present study, we tested the hypothesis that increased cocaine self-administration with extended access was associated with increased activity of the κ opioid system in rats.

Materials and methods

Rats self-administered 0.5 mg/kg per injection of cocaine on a fixed-ratio (FR) schedule in either 1-h (short access, ShA) or 6-h (long access, LgA) sessions. After cocaine intake in the LgA rats increased to a maximum, the effects of κ opioid receptor antagonists and a partial agonist were tested on cocaine intake in ShA and LgA rats.

Results

Cocaine self-administration increased under FR and progressive-ratio (PR) schedules in LgA rats. Nor-BNI (15–30 mg/kg), a κ receptor antagonist, decreased cocaine intake in LgA rats under a PR schedule (ShA, +1.7%; LgA, −27.4% from baseline), whereas naltrexone (0.3–10 mg/kg) and SG-II-49 (0.025–0.1 mg/kg), a nonspecific opioid receptor antagonist and a partial agonist, respectively, decreased cocaine intake in both groups (PR data: SG-II-49, ShA −28.6%, LgA −19.8%; naltrexone, ShA −34.6%, LgA −11.8% compared with vehicle data).

Conclusions

The present study demonstrated that the antagonism of κ opioid receptors attenuated only the increased cocaine intake in LgA rats under a PR schedule, whereas the antagonism of µ and κ receptors decreased cocaine intake in both ShA and LgA groups. The data suggest that increased motivation for cocaine in rats with extended access may be related to increased κ opioid activity and may contribute to compulsive use.

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Acknowledgements

We gratefully acknowledge the technical assistance of Jovy Quiocho who was an undergraduate student of the University of California, San Diego. This is publication number 20047 from The Scripps Research Institute. This study was supported by the National Institute on Drug Abuse grant DA004398 (G.F.K.) and the National Institute on Alcohol and Alcoholism grant AA016029 (J.R.C.).

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Authors and Affiliations

  1. Committee on the Neurobiology of Addictive Disorders SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA

    Sunmee Wee, Laura Orio & George F. Koob

  2. Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA, USA

    Senait Ghirmai & John R. Cashman

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  1. Sunmee Wee
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  2. Laura Orio
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  3. Senait Ghirmai
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Correspondence to Sunmee Wee.

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Wee, S., Orio, L., Ghirmai, S. et al. Inhibition of kappa opioid receptors attenuated increased cocaine intake in rats with extended access to cocaine. Psychopharmacology 205, 565–575 (2009). https://doi.org/10.1007/s00213-009-1563-y

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  • DOI: https://doi.org/10.1007/s00213-009-1563-y

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