Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice

Tung-Yen Lee; Pei-Lu Yi; Fang-Chia Chang

doi:10.3389/fpsyt.2023.1196994

Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice

Front Psychiatry. 2023 Jun 29:14:1196994. doi: 10.3389/fpsyt.2023.1196994. eCollection 2023.

Authors

Tung-Yen Lee¹, Pei-Lu Yi², Fang-Chia Chang^{1

3

4

5

6}

Affiliations

¹ Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Sport Management, College of Tourism, Leisure and Sports, Aletheia University, Taipei, Taiwan.
³ Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
⁴ Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan.
⁵ Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung City, Taiwan.
⁶ Department of Medicine, College of Medicine, China Medical University, Taichung City, Taiwan.

Abstract

Introduction: Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originates from the lateral hypothalamic area (LHA) and projects diffusely to the whole brain, and hypocretin may be involved in the features of stress-related disorder, PTSD.

Methods: Our study aimed to investigate the role of basolateral amygdala (BLA) hypocretin signals in the pathophysiology of PTSD-like symptoms induced by the modified multiple-prolonged stress (MPS) protocol. The BLA, a brain region involved in fear-related behaviors, receives the hypocretin projections. In this study, TCS1102, a dual hypocretin receptor antagonist, was used to block the hypocretin signal in BLA.

Results: Our data indicated that the MPS protocol is a potential PTSD-like paradigm in mice. Meanwhile, the blockade of hypocretin signaling in the BLA relieved the MPS-induced fear response, and partially reduced PTSD-like anxiety behaviors performed by the open field test (OFT) and elevated plus maze (EPM) task.

Discussion: Our findings suggest that the hypocretinergic system is a potential therapeutic approach for PTSD treatment. With further research, the hypocretin-based medication can be a candidate for human PTSD treatment.

Keywords: PTSD; amygdala; anxiety; fear memory; hypocretin; lateral hypothalamic area (LHA); multiple prolonged stress (MPS).