The Ventrolateral Periaqueductal Gray Contributes to Depressive-Like Behaviors in Recovery of Inflammatory Bowel Disease Rat Model

Chih-Yuan Ko; Ya-Bi Yang; Dylan Chou; Jian-Hua Xu

doi:10.3389/fnins.2020.00254

The Ventrolateral Periaqueductal Gray Contributes to Depressive-Like Behaviors in Recovery of Inflammatory Bowel Disease Rat Model

Front Neurosci. 2020 Mar 24:14:254. doi: 10.3389/fnins.2020.00254. eCollection 2020.

Authors

Chih-Yuan Ko^{1

2

3

4}, Ya-Bi Yang⁵, Dylan Chou⁶, Jian-Hua Xu⁷

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
² Department of Clinical Nutrition, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
³ Respiratory Medicine Center of Fujian Province, Quanzhou, China.
⁴ The Sleep Medicine Key Laboratory of Fujian Medical Universities, Fujian Province University, Quanzhou, China.
⁵ Physical Examination Center, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.
⁶ Department of Physiology, Zunyi Medical University, Zhuhai, China.
⁷ Department of Tumor Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

Abstract

Background: Patients with inflammatory bowel disease (IBD) experience depression, even in the remission phase of IBD symptoms. Although mapping depression-associated brain regions through the gut-brain axis can contribute to understanding the process, the mechanisms remain unclear. Our previous results support the idea that glutamatergic transmission in the ventrolateral periaqueductal gray (vlPAG) mediates stress-induced depression-like behaviors. Thus, we hypothesize that the vlPAG plays a role in regulating depression during remission of IBD.

Methods: We used dextran sulfate sodium (DSS)-induced visceral pain model to evoke depression-like behaviors, assessed by tail suspension test (TST) and sucrose preference test (SPT), and electrophysiological recordings from vlPAG.

Results: Symptoms of animals modeling IBD were relieved by replacing DSS solution with normal drinking water, but their depression-like behaviors sustained. Moreover, the impairment of glutamatergic neurotransmission in vlPAG was sustained as well. Pharmacologically, microinfusion of the glutamate receptor 1 (GluR1) antagonist NASPM into vlPAG mimicked the depression-like behaviors. Furthermore, intra-vlPAG application of AMPA and AMPA receptor-mediated antidepressant (2R,6R)-hydroxynorketamine [(2R,6R)-HNK] reversed the DSS-induced depression-like behaviors in the remission phase of visceral abnormalities.

Conclusion: Our results suggest that vlPAG glutamatergic transmission mediates depression-like behaviors during remission of DSS-induced visceral pain, suggesting that vlPAG mapping to the gut-brain axis contributes to depression during remission of IBD.

Keywords: (2R; 6R)-hydroxynorketamine; depression; electrophysiology; inflammatory bowel diseases; periaqueductal gray; visceral pain.