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). 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. 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.

中文翻译：

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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以及相关脑区多巴胺 D1 和 GABAA 受体的变化

中年女性，尤其是围绝经期女性，易患抑郁症，但潜在机制尚不清楚。多巴胺能和 GABA 能系统功能障碍与抑郁症的病理生理学有关。在目前的研究中，我们分别使用 2 个月大和 11 个月大的 C57BL/6 小鼠作为年轻和中年小鼠。慢性固定压力（CIS）被用来诱导抑郁样行为，而蔗糖偏好测试（SPT）、悬尾测试（TST）和强迫游泳测试（FST）被用来评估这些行为。然后我们测量了伏隔核 (NAc) 和前额叶皮层 (PFC) 中多巴胺受体 D1 (DRD1) 和 GABAA 受体 GABRA1、GABRB2 和 GABRG2 的 mRNA 水平。我们发现，与中年对照小鼠和年轻小鼠相比，中年小鼠的 FST 不动时间显着增加。此外，与中年对照小鼠相比，中年小鼠对蔗糖水的偏好降低。然而，在我们的行为测试中，独联体并没有引起幼鼠表现的明显变化。此外，中年小鼠在没有压力的情况下表现出与年轻小鼠相同的不动时间。在没有压力的情况下，在中年小鼠的 NAc 和 PFC 中发现了 DRD1、GABRA1 和 GABRB2 的 mRNA 水平下降，但没有发现 GABRG2。在接受 CIS 的中年小鼠中发现 NAc 中 DRD1 和 NAc 和 PFC 中 GABRG2 的 mRNA 水平进一步降低。我们的研究结果表明，在没有压力的情况下，衰老不能直接诱发抑郁。然而，在压力存在的情况下，衰老可能会导致中年小鼠对抑郁症的易感性。在这种情况下，CIS 诱导的 DRD1 和 GABRG2 水平的降低可能与抑郁症易感性的增加有关。