A novel stress re-stress model: modification of re-stressor cue induces long-lasting post-traumatic stress disorder-like symptoms in rats

Abstract

Background: Post-traumatic stress disorder (PTSD) develops after exposure to a severe traumatic event. Stress re-stress (SRS) model of PTSD using forced swim as a re-stress shows hypocortisolism, an index of hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Despite this, the SRS model lacks development of hyperarousal and intrusive memory which are prominent symptoms of PTSD.

Aim: Developing a model which shows more clinical similarities to PTSD. We used intense foot-shock (FS) (2 mA for 10 sec) instead of the forced-swim test (FST) as a re-stress cue.

Methods: The stress session was performed on D-2 except control group. The FST group rats were forced to swim for 20 min, and FS group rats were exposed to foot shock of 2 mA for 10 sec. The re-stress sessions of FST and FS were performed on D-8, 14, 20, 26 and 32. The freezing behavior was evaluated after the FS re-stress cue, and remaining behavioral assessments such as anxiety and depressive-like behavior, and cognitive dysfunction were performed on last day of the experiment.

Results: The FS-induced PTSD-like (anxiety and depressive-like behavior, and cognitive dysfunction) symptoms and a decrease in plasma corticosterone were more significant compared to FST. The hyperarousal and intrusive memory induced by FS were additional symptoms in the SRS model. Treatment with paroxetine significantly attenuated FST and FS-induced behavioral deficits in PTSD rats.

Conclusion: FS as a re-stress model shows prominent PTSD-like symptoms with HPA axis dysfunction compared to FST.

Keywords:

• Post-traumatic stress disorder
• stress re-stress
• forced swim test
• foot shock
• corticosterone
• paroxetine

View correction statement:

Correction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

All animal experiments were performed according to the principles guidelines of National Research Council US Committee for the Update of the Guide for the Care and Use of Laboratory Animals 2011. All the experimental methods were approved by the Institutional animal ethical committee, Banaras Hindu University (Approval No.: Dean/2016/CAEC/37).

Additional information

Funding

Teaching assistantship and student fellowship from MHRD through Indian Institute of Technology (Banaras Hindu University).

Notes on contributors

Santosh Kumar Prajapati

Santosh Kumar Prajapati and Neha Singh conducted the study and analyzed the results. Debapriya Garabadu helped in experimental work. Sairam Krishnamurthy and Santosh Kumar Prajapati wrote and checked the manuscript. Sairam Krishnamurthy designed the study and analysed the results.