Susceptibility to chronic immobilization stress-induced depressive-like behaviour in middle-aged female mice and accompanying changes in dopamine D1 and GABAA receptors in related brain regions.

IF 4.7 2区 心理学 Q1 BEHAVIORAL SCIENCES Behavioral and Brain Functions Pub Date : 2021-04-16 DOI:10.1186/s12993-021-00175-z
Guofen Cao, Gaili Meng, Li Zhu, Jie Zhu, Nan Dong, Xiaolan Zhou, Sumei Zhang, Yongai Zhang
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引用次数: 1

Abstract

Background: Middle-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).

Results: We 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.

Conclusions: Our 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.

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中年雌性小鼠对慢性固定应激诱导的抑郁样行为的易感性及相关脑区多巴胺D1和GABAA受体的变化
背景:中年女性,尤其是围绝经期女性易患抑郁症,但其潜在机制尚不清楚。多巴胺能和gaba能系统功能障碍与抑郁症的病理生理有关。在本研究中,我们将2月龄和11月龄的C57BL/6小鼠分别作为青年和中年小鼠。采用慢性固定应激(CIS)诱导抑郁样行为,并采用蔗糖偏好试验(SPT)、悬尾试验(TST)和强迫游泳试验(FST)评估这些行为。然后,我们测量了伏隔核(NAc)和前额皮质(PFC)中多巴胺受体D1 (DRD1)和GABAA受体GABRA1、GABRB2和GABRG2的mRNA水平。结果:我们发现,与中年对照小鼠和青年小鼠相比,中年小鼠在FST的静止时间明显增加。此外,与中年对照组小鼠相比,中年小鼠对蔗糖水的偏好有所降低。然而,在我们的行为测试中,CIS并没有引起幼鼠表现的明显变化。此外,在没有压力的情况下,中年小鼠表现出与年轻小鼠相同的静止时间。在无应激状态下,中年小鼠NAc和PFC中DRD1、GABRA1和GABRB2 mRNA水平下降,而GABRG2 mRNA水平未见下降。CIS处理的中年小鼠NAc中DRD1和NAc和PFC中GABRG2的mRNA水平进一步降低。结论:我们的研究结果表明,在没有压力的情况下,衰老不会直接导致抑郁。然而,衰老可能导致中年老鼠在压力下容易抑郁。在这种情况下,cis诱导的DRD1和GABRG2水平的降低可能与抑郁易感性的增加有关。
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来源期刊
Behavioral and Brain Functions
Behavioral and Brain Functions 医学-行为科学
CiteScore
5.90
自引率
0.00%
发文量
11
审稿时长
6-12 weeks
期刊介绍: A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.
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