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Chronic mild stress induces behavioral and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats

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Abstract

Rationale

Interactions among stress, serotonin 1A (5-HT1A) receptors, and the hypothalamic–pituitary–adrenocortical (HPA) system have been proposed to influence the development of depression in humans. The investigation of depression-relevant behaviors and physiological responses to environmental stressors in animal models of depression may provide valuable insight regarding these mechanisms.

Objectives

The purpose of these experiments was to investigate the interactions among central 5-HT1A receptors, endocrine function, and behavior in an animal model of depression, chronic mild stress (CMS).

Methods

The current study examined behavioral responses to a pleasurable stimulus (sucrose), estrous cycle length (in female rats), and plasma hormone levels following systemic administration of a selective 5-HT1A receptor agonist [(+)8-hydroxy-N,N-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT); 40 μg/kg, s.c.; administered 15 min prior to sacrifice], in male and female rats exposed to 4 weeks of CMS.

Results

Four weeks of CMS produced a reduction in the intake of 1% sucrose (anhedonia), as well as attenuated adrenocorticotropic hormone (ACTH) responses to 8-OH-DPAT in both male and female rats (22 and 18% lower than the control groups, respectively). Corticosterone and oxytocin responses to 8-OH-DPAT were not altered by exposure to CMS. In female rats, CMS induced a lengthening of the estrous cycle by ∼40%.

Conclusions

CMS produces minor HPA disruptions along with behavioral disruptions. Alterations in 5-HT1A receptor function in specific populations of neurons in the central nervous system may be associated with the CMS model. The current findings contribute to our understanding of the relations that stress and neuroendocrine function have to depressive disorders.

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Acknowledgements

This research is published in memory of Dr. Louis D. Van de Kar. The authors are grateful for his guidance and friendship, and he is greatly missed. This research was supported by United States Public Health Service grants NS34154 and MH58448. Oxytocin antiserum was donated by Dr. Lanny C. Keil (NASA Ames Research Center, Moffat Field, CA). The authors would like to thank Dr. Lydia DonCarlos and Mr. Brett Peterson for assistance. All experimental procedures comply with current laws of the United States of America.

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Authors and Affiliations

  1. Department of Pharmacology and Center for Serotonin Disorders Research, Loyola University of Chicago, 2160 South First Avenue, Maywood, IL, 60153, USA

    Angela J. Grippo, Nicole R. Sullivan, Katerina J. Damjanoska, James W. Crane, Gonzalo A. Carrasco, Ju Shi, Zhuo Chen, Francisca Garcia, Nancy A. Muma & Louis D. Van de Kar

  2. Department of Psychiatry, University of Illinois at Chicago, 1601 W. Taylor Street (M/C 912), Chicago, IL, 60612, USA

    Angela J. Grippo

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  1. Angela J. Grippo
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  2. Nicole R. Sullivan
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  3. Katerina J. Damjanoska
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  4. James W. Crane
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  5. Gonzalo A. Carrasco
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  6. Ju Shi
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  9. Nancy A. Muma
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  10. Louis D. Van de Kar
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Correspondence to Angela J. Grippo.

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Grippo, A.J., Sullivan, N.R., Damjanoska, K.J. et al. Chronic mild stress induces behavioral and physiological changes, and may alter serotonin 1A receptor function, in male and cycling female rats. Psychopharmacology 179, 769–780 (2005). https://doi.org/10.1007/s00213-004-2103-4

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  • DOI: https://doi.org/10.1007/s00213-004-2103-4

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