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Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse

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Abstract

Rationale

Women have twice the risk as men to develop depression. Approximately, 24% of major depression disorder cases have comorbid disorders with substance abuse. Several central systems, including dopaminergic and serotonergic pathways, are thought to be involved in such comorbidity.

Objectives

The present study established a chronic social stress model in female rats, which produces some cardinal features of depressive-like symptoms. Further, we examined the effects of acute cocaine on dopamine (DA) and serotonin (5-HT) in the nucleus accumbens (NAc) using this model.

Methods

Female Long-Evans rats confronted a nursing dam in its home cage for 30 min twice daily for 21 days. The non-stressed control group was handled daily throughout the experiment. During the 21 days of stress, behaviors during confrontations, weight, preference for saccharin, and estrous cycles were measured. Ten days after the last confrontation, the experimental rat was challenged with 10 mg/kg of cocaine, and levels of DA and 5-HT in the NAc were measured using in vivo microdialysis.

Results

During the course of daily confrontations for 21 days, the experimental females significantly increased the duration of immobility, reduced weight gain and the preference for saccharin, and disrupted estrous cycles during the stress. Chronic social stress significantly attenuated cocaine-induced DA levels, and to some extent, attenuated a percent change of 5-HT compared to the non-stressed control group.

Conclusions

Chronic social defeat stress for 21 days induced physiological and behavioral depression-relevant deficits and blunted response of dopaminergic and to some extent, serotonergic neurons to cocaine challenge in females.

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Acknowledgements

The present work was supported by NIDA DA 002632. We would like to thank Dr. L. Michael Romero and Ms. Brittany Slabach from Department of Biology, Tufts University for their guidance with the CORT assay. We also appreciate Messrs. Eric Sorensen, Daniel M. Pasternack, Mss. Jessica Xia, Manting Chiang, Rosemary Trumbull, and Lindsay Kneen for conducting the stress protocol.

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Authors and Affiliations

  1. Department of Psychology, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA, 02155, USA

    Akiko Shimamoto, Joseph F. DeBold, Elizabeth N. Holly & Klaus A. Miczek

  2. Departments of Psychiatry, Pharmacology and Neuroscience, Tufts University, 145 Harrison Avenue, Boston, MA, 02111, USA

    Klaus A. Miczek

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  1. Akiko Shimamoto
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  2. Joseph F. DeBold
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  3. Elizabeth N. Holly
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  4. Klaus A. Miczek
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Correspondence to Akiko Shimamoto.

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Shimamoto, A., DeBold, J.F., Holly, E.N. et al. Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse. Psychopharmacology 218, 271–279 (2011). https://doi.org/10.1007/s00213-011-2364-7

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