IMR Press / JIN / Volume 22 / Issue 2 / DOI: 10.31083/j.jin2202043
Open Access Original Research
Dynamic Changes of Behavioral Despair, HPA Axis Activity, and Hippocampal Neurogenesis in Male Rats Induced by Social Defeat Stress
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1 Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180 Fukuoka, Japan
2 Division of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 670-8524 Hyogo, Japan
3 Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, 814-0180 Fukuoka, Japan
*Correspondence: (Masayoshi Mori)
J. Integr. Neurosci. 2023, 22(2), 43;
Submitted: 11 October 2022 | Revised: 28 November 2022 | Accepted: 2 December 2022 | Published: 20 February 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Psychosocial stress factors, such as threat and defeat, are major risk factors for the development of depression. The precise mechanisms underlying stress-induced depression are not clearly understood because the stress response in the brain varies in a stress-frequency-dependent manner. In the current research milieu on the pathogenesis of depression, the focus is on depression-like behavioral phenotype, hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis. However, most studies have evaluated the symptomatic features of depression at certain time points after exposure to psychosocial stress. Here, we examined the frequency-dependent effects of psychosocial stress on depression-related features in rats. Methods: In the present study, different frequencies (one, two, three, or four times) of psychosocial stress were applied to 19 male Sprague-Dawley rats using a resident/intruder paradigm. Subsequently, the rats were subjected to a stress reactivity test to evaluate HPA axis activity, following which assessments of immobility behavior in the forced swimming test (FST) and adult neurogenesis were conducted. Results: One-time stressed rats showed a decrease in immobility behavior in the FST and the amount of doublecortin (DCX)-positive cells. Two-time stress caused hypoactivity of the HPA axis. In contrast, immobility behavior and HPA axis activity were increased after four-time stress exposure, but the number of DCX-positive cells was decreased. Conclusions: Our findings suggest that psychosocial stress produces a biphasic effect on the symptoms of depression in a stress-frequency-dependent manner, which could provide insights to facilitate further pathogenesis research on depression.

social defeat
stress frequency
hippocampal neurogenesis
hypothalamic-pituitary-adrenal axis
20K16657/Japan Society for the Promotion of Science (JSPS) KAKENHI
Fig. 1.
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