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A dysphoric-like state during early withdrawal from extended access to methamphetamine self-administration in rats

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Abstract

Rationale

Negative emotional states during drug withdrawal may contribute to compulsive drug intake and seeking in humans. Studies suggest that extended access to methamphetamine induces compulsive drug intake in rats.

Objective

The present study tested the hypothesis that compulsive methamphetamine intake in rats with extended access is associated with negative emotional states during drug withdrawal.

Methods

Rats with short (1 h, ShA) and extended access (6 h, LgA) to methamphetamine self-administration (0.05 mg/kg/infusion) were tested for reward thresholds using intracranial self-stimulation (ICSS). Different groups of ShA and LgA rats were examined for depression-like and anxiety-like states in the novelty-suppressed feeding, open field, defensive burying, and forced swim tests.

Results

With extended access, ICSS thresholds gradually increased, which was correlated with the increase of drug intake. During drug withdrawal, the increased ICSS thresholds returned to levels observed before exposure to extended access to methamphetamine. Upon re-exposure to extended access to methamphetamine, ICSS thresholds showed a more rapid escalation than during the initial exposure. LgA rats showed a longer latency to approach chow in the center of a novel field and remained immobile longer in the forced swim test than ShA rats did during early withdrawal. In contrast, ShA rats actively buried an aversive shock probe whereas LgA rats remained immobile in the defensive burying test.

Conclusion

The data suggest that extended access to methamphetamine produces a more depressive-like state than anxiety-like state in rats during early withdrawal.

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Acknowledgments

We gratefully acknowledge the technical assistance of Jovy Quiocho, Anjali Samant, Nicole Ng, and Tali Nadav who were undergraduate students of the University of California in San Diego in the self-administration and self-stimulation. We also thank Clay Archer, Robert Lintz, and Mike Arends for the technical and editorial assistance. This is publication number 21070 from The Scripps Research Institute. This study was supported by National Institute on Drug Abuse grant DA010072 (G.F.K), National Research Foundation of Korea grant NRF-2009-013-E00056 (C.G.J), Brain Research Center of the 21st Century Frontier Research Program grant 2010K000812 (C.G.J) funded by the MEST, Republic of Korea, The Pearson Center for Alcoholism and Addiction Research, and a Veterans Health Administration Research Career Scientist Award (GS).

Conflict of interest

All the authors declare that there is no relationship with the organization supporting this research and no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea

    Choon-Gon Jang

  2. Research Service, VA San Diego Healthcare System, and Department of Anesthesiology, School of Medicine, University of California, San Diego, CA, USA

    Gery Schulteis

  3. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, San Diego, CA, USA

    Timothy Whitfield, George F. Koob & Sunmee Wee

  4. Department of Molecular Therapeutics, Scripps Florida, 130 Scripps Way, Jupiter, FL, 33458, USA

    Sunmee Wee

Authors
  1. Choon-Gon Jang
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  2. Timothy Whitfield
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  3. Gery Schulteis
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  4. George F. Koob
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  5. Sunmee Wee
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Correspondence to Sunmee Wee.

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Jang, CG., Whitfield, T., Schulteis, G. et al. A dysphoric-like state during early withdrawal from extended access to methamphetamine self-administration in rats. Psychopharmacology 225, 753–763 (2013). https://doi.org/10.1007/s00213-012-2864-0

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  • DOI: https://doi.org/10.1007/s00213-012-2864-0

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