Brain Neural Activity Patterns in an Animal Model of Antidepressant-Induced Manic Episodes.

Min Chen,Xueqin Song,Guangqian Dou,Ziyao Cai,Jingjing Zhu,Guangdong Chen,Chuanxin Liu,Jing Ping,Xiaodong Lin,Ce Chen,Chuanjun Zhuo,Chunmian Chen,Hongjun Tian,Tao Fang,Langlang Cheng,Feifei Zhao,Suling Chen,Weihua Yue

doi:10.3389/fnbeh.2021.771975

Abstract

Background: In the treatment of patients with bipolar disorder (BP), antidepressant-induced mania is usually observed. The rate of phase switching (from depressive to manic) in these patients exceeds 22%. The exploration of brain activity patterns during an antidepressant-induced manic phase may aid the development of strategies to reduce the phase-switching rate. The use of a murine model to explore brain activity patterns in depressive and manic phases can help us to understandthe pathological features of BP. The novel object recognition preference ratio is used to assess cognitive ability in such models.Objective: To investigate brain Ca2+ activity and behavioral expression in the depressive and manic phases in the same murine model, to aid understanding of brain activity patterns in phase switching in BP.Methods: In vivo two-photon imaging was used to observe brain activity alterations in a murine model in which induce depressive-like and manic-like behaviors were induced sequentially. The immobility time was used to assess depressive-like symptoms and the total distance traveled was used to assess manic-like symptoms.Results: In vivo two-photon imaging revealed significantly reduced brain Ca2+ activity in temporal cortex pyramidal neurons in the depressive phase in mice exposed to chronic unpredictable mild stress compared with naïve controls. The brain Ca2+ activity correlated negatively with the novel object recognition preference ratio within the immobility time. Significantly increased brain Ca2+ activity was observed in the ketamine-induced manic phase. However, this activity did not correlate with the total distance traveled. The novel object recognition preference ratio correlated negatively with the total distance traveled in the manic phase.

Highlights

MATERIALS AND METHODSBipolar disorder (BP) is a chronic psychiatric disorder affecting more than 1–4% of the global population (Grande et al, 2016)
Such models are suitable for the examination of brain activity features in the antidepressant-induced manic phase of bipolar disorder (BP), as they often involve the use of ketamine to induce mania (Liu et al, 2018; Bhatt et al, 2021; Gao et al, 2021)
Mice exposed to chronic unpredictable mild stress (CUMS) had significantly longer immobility times in the depressive phase (P < 0.001; Figure 1C) and significantly longer total distances traveled in the manic phase (P < 0.001; Figure 2C)

Summary

Introduction

MATERIALS AND METHODSBipolar disorder (BP) is a chronic psychiatric disorder affecting more than 1–4% of the global population (Grande et al, 2016). Hypotheses regarding specific disturbances of brain neural activity, circuits, and networks in patients with BP have been supported by macro-neuroimaging studies, especially those in which functional magnetic resonance imaging (MRI) and electroencephalography (EEG) have been used (Berk, 2009; Berk et al, 2011, 2014; Fries et al, 2012; Schneider et al, 2012) These studies have demonstrated that brain alterations and cognitive impairment are consistently associated not with the timing of first BP episodes (whether depressive or manic), but with repeated manic or depressive episodes (El-Badri et al, 2001; Strakowski et al, 2002; Lyoo et al, 2006; Robinson and Ferrier, 2006). Objective: To investigate brain Ca2+ activity and behavioral expression in the depressive and manic phases in the same murine model, to aid understanding of brain activity patterns in phase switching in BP

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