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Abstinence from repeated amphetamine treatment induces depressive-like behaviors and oxidative damage in rat brain

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Abstract

Rationale

Amphetamine has a significant potential for abuse and addiction. Among prolonged abusers, amphetamine withdrawal-induced depressive symptoms are common; however, their pathophysiological mechanism is not fully understood. Previously, we found that repeated treatment with amphetamine for 2 weeks induced oxidative stress in rat brain.

Objectives

The purpose of the current study is to analyze whether abstinence from repeated amphetamine treatment in rats induces depressive-like behaviors and if oxidative damage in the brain continues during abstinence.

Methods

Rats were given repeated treatment with amphetamine once daily at 1, 2, or 4 mg/kg for 14 days. From 10 to 14 days after final amphetamine treatment, behavioral changes were monitored using open field test, novel object recognition test, and forced swim test. Oxidative damage in the medial frontal cortex and hippocampus was analyzed by immunohistochemistry.

Results

We found that drug abstinence after repeated amphetamine stimulation decreased locomotor activity and exploratory behavior in the open field test, increased immobility in the forced swim test, and had no significant effect on the recognition index in the novel object recognition test. We also found that amphetamine abstinence increased levels of 4-hydroxynonenal–protein adducts and 8-hydroxyguanosine in rat medial frontal cortex and in CA3 and dentate gyrus regions of the hippocampus.

Conclusions

These results suggest that amphetamine abstinence displays depressive-like behaviors in rats and induces oxidative damage to lipids and RNA in rat brain. Our findings indicate that the process of oxidative stress may play a role in pathophysiological changes during drug abstinence from repeated amphetamine stimulation.

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Acknowledgments

This work is supported by a Manitoba Health Research Council Establishment grant to JF Wang. This work is also supported by one Canadian Institutes of Health Research (CIHR) operating grant to JF Wang, and another CIHR operating grant to LT Young, AC Andreazza and JF Wang.

Conflict of interest

The authors declare no conflict of interest. In addition to his primary employer, Dr. Trevor Young is an occasional speaker for Eli Lilly and AstraZeneca.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, 406 - 753 McDermot Ave., Winnipeg, Manitoba, R3E 0T6, Canada

    Hua Tan & Jun-Feng Wang

  2. Department of Psychiatry, University of Manitoba, Winnipeg, Canada

    Jun-Feng Wang

  3. Department of Psychiatry, University of British Columbia, Vancouver, Canada

    Yi Che & Jun-Feng Wang

  4. Medical College of Soochow University, Suzhou, People’s Republic of China

    Yi Che & Yong-Hua Cui

  5. Department of Psychiatry, University of Toronto, Toronto, Canada

    Ana C. Andreazza & L. Trevor Young

Authors
  1. Yi Che
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  2. Yong-Hua Cui
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  3. Hua Tan
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  4. Ana C. Andreazza
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  5. L. Trevor Young
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  6. Jun-Feng Wang
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Correspondence to Jun-Feng Wang.

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Che, Y., Cui, YH., Tan, H. et al. Abstinence from repeated amphetamine treatment induces depressive-like behaviors and oxidative damage in rat brain. Psychopharmacology 227, 605–614 (2013). https://doi.org/10.1007/s00213-013-2993-0

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  • DOI: https://doi.org/10.1007/s00213-013-2993-0

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