Depression is a prevalent disease in modern society, and has been linked to stressful events at early ages. Women are more susceptible to depression, and the neural basis for this are still under investigation. Serotonin is known to be involved in depression, and a decrease in 5HT_1A expression is observed on temporal and cortical areas in both men and women with depression. As knockout animals for TREK-1 are resilient to depression, this channel has emerged as a new potential pharmacological target for depression treatment. In this study, maternal separation (MS) was used to emulate early-life stress, and evaluate behaviour, as well as TREK-1 and 5HT_1A expression in the brain using immunohistochemistry. In juvenile females, 5HT_1A reduction coupled to increased TREK-1 in the dentate gyrus (DG) was associated with behavioural despair, as well as increased TREK-1 expression in basolateral amygdala (BLA) and prelimbic cortex (PL). In juvenile males, MS induced an increase in 5HT_1A in the BLA, and in TREK-1 in the PL, while no behavioural despair was observed. Anhedonia and anxiety-like behaviour were not induced by MS. We conclude stress-induced increase in TREK-1 in PL and GD is associated to depression, while 5HT_1A changes coupled to TREK-1 changes may be necessary to induce depression, with females being more vulnerable to MS effects than males. Thus, TREK-1 and 5HT_1A may be potential pharmacological targets for antidepressants development.

抑郁症是现代社会的一种普遍疾病，并且与早年的压力事件有关。女性更容易患抑郁症，其神经基础仍在调查中。已知血清素与抑郁症有关，并且在患有抑郁症的男性和女性的颞区和皮质区观察到5HT _1A表达的减少。由于 TREK-1 基因敲除动物对抑郁症具有抵抗力，因此该通道已成为抑郁症治疗的新潜在药理学靶点。在这项研究中，母体分离 (MS) 用于模拟早期生活压力，并使用免疫组织化学评估行为以及大脑中的TREK-1 和 5HT _1A表达。在幼年雌性中，5HT _1A齿状回 (DG) 中 TREK-1 增加的减少与行为绝望以及基底外侧杏仁核 (BLA) 和前边缘皮层 (PL) 中 TREK-1 表达的增加有关。在幼年雄性中，MS 诱导BLA中的 5HT _1A和 PL 中的 TREK-1 增加，而没有观察到行为绝望。MS 不会诱发快感缺失和焦虑样行为。我们得出结论，压力引起的 PL 和 GD 中 TREK-1 的增加与抑郁症有关，而与 TREK-1 变化相关的 5HT _1A变化可能是诱发抑郁症所必需的，女性比男性更容易受到 MS 影响。因此，TREK-1 和 5HT _1A可能是抗抑郁药开发的潜在药理学靶点。