Hong Tan1,2 · Shizhen Jin1,2 · Wenjin Lv1,2 · Lingyu Guo1,2 · Peiran Jiang3  · Yongjian Li2  · Mengjia Shi2  · Danting Wang2  · Yongcheng Wang2  · Aimin Bao1,2,3,4

1 Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China 

2 NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Centre for Brain Research and Brain‑Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou 310000, China 

3 National Brain Bank for Health and Disease, Zhejiang University, Hangzhou 310000, China 

4 Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou 310003, China

Abstract

Clinical studies have suggested that increased plasma oxytocin (OT) levels are a promising biomarker for bipolar disorder (BD), and our earlier post-mortem study found increased OT activity in the hypothalamic paraventricular nucleus (OT^PVN) in BD. However, the potential contribution of the supraoptic nucleus (SON, OT^SON), a major part of the central OT system, to BD remains unknown. We therefore systematically performed independent acute or chronic chemogenetic activation of OT^PVN, OT^SON, or OT^PVN+SON experiments in OT-cre mice. We found that acute activation of OT^PVN+SON neurons led to slight mania-like (anti-depression-like) behaviors both in male and female mice, while chronic activation of OT^PVN or OT^PVN+SON led to sex-dependent behavioural changes from depression/anxiety-like to mania-like, accompanied by stress-related molecular changes in a sex- dependent manner in the medial prefrontal cortex. Our findings imply that OT may be involved in bipolar-like mood changes in a sex- and dosage-dependent manner.

Keywords

Oxytocin; Bipolar disorder; Hypothalamus; Medial prefrontal cortex; Chemogenetics

[SpringerLink]