Susceptibility to chronic immobilization stress\u2010induced depressive-like behaviour in middle\u2010aged female mice and accompanying changes in dopamine D1 and GABAA receptors in related brain regions

Gaili Meng,Jie Zhu,Yongai Zhang,Guofen Cao,Sumei Zhang,Xiaolan Zhou,Li Zhu,Nan Dong

doi:10.1186/s12993-021-00175-z

Abstract

BackgroundMiddle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC).ResultsWe found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS.ConclusionsOur results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.

Highlights

Depression has become the leading cause of disability worldwide [1,2,3]
Chronic immobilization stress (CIS)‐induced susceptibility to depressive‐like behaviour in middle‐aged mice There was a significant effect of age [F(1, 32) = 4.582, P < 0.05] and CIS exposure [F(1, 32) = 7.810, P < 0.05] but not an interaction effect [F(1, 32) = 1.896, P > 0.05] on performance in the forced swim test (FST)
CIS had no effect on immobility in the two young groups of mice, as indicated by the similar immobility times in the FST

Summary

Introduction

Depression has become the leading cause of disability worldwide [1,2,3]. The incidence of depression is obviously sex-dependent [4, 5]. The incidence of depression is obviously age-dependent. Especially during perimenopause, which occurs in the final years of the female reproductive stage, the rates of major depressive disorder and clinical depression symptoms increase two- to threefold in women [6]. These human data indicate the importance of ageing in susceptibility to depression in middle age in women. Few studies have investigated the effect of stress exposure and the mechanisms underlying susceptibility to depression in middle age. Middle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. We measured the mRNA levels of dopamine receptor D1 (DRD1) and the G ABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC)

Methods

Results

Discussion

Conclusion