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

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-HT 1A 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. © Springer-Verlag 2004.