Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression
Voluntary running influences the efficacy of fluoxetine in a model of postpartum depression
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DOI：
10.1016/j.neuropharm.2017.09.017
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发表时间：
2018-01-01
影响因子：
4.7
通讯作者：
Galea, Liisa A. M.
中科院分区：
文献类型：
--
作者：
Gobinath, Aarthi R.;Richardson, Robin J.;Galea, Liisa A. M.
大约 15% 的母亲患有产后抑郁症。不幸的是，产后抑郁症的治疗选择是有限的。氟西汀 (FLX) 等药理抗抑郁药可能存在争议，因为产后疗效证据尚不明确，而且担心新生儿接触抗抑郁药。另外，运动等非药物抗抑郁药可能争议较少，但其对产后抑郁症的疗效尚不清楚。为了研究这一点，我们每天用高水平的皮质酮（CORT；40 mg/kg）治疗大鼠，以在产后期诱导抑郁样表型或油（CORT 的载体）。在油和 CORT 条件下，创建了四种额外的抗抑郁条件： 1. FLX (10 mg/kg) + 运动（自愿使用跑步轮）； 2.FLX+不运动； 3、生理盐水（FLX用载体）+运动； 4.盐水+不运动。我们检查了产妇护理、抑郁样和焦虑样行为、压力反应；海马神经发生和水坝被分类为“高跑”或“低跑”。 FLX 治疗，无论是单独治疗还是与高跑结合治疗，都可以防止 CORT 引起的孕产妇护理中断。正如预期的那样，CORT 增加了抑郁样行为，但运动，无论跑步量如何，都会减少抑郁样行为。有趣的是，FLX（而不是 CORT）增加了焦虑样行为，而同时运动并不能缓解这种行为。 FLX 治疗略微但显着地促进了强迫游泳应激后血清 CORT 的恢复。单独的 CORT 和 FLX 会减少神经发生，而运动与 FLX 结合会增加双皮质素表达细胞的密度。与对照组相比，高跑增加了双皮质素表达细胞（未成熟神经元）的密度。总的来说，这些发现表明 FLX 和运动可以逆转母鼠抑郁症的不同内表型，这对于调查产后抑郁症的治疗方案具有转化意义。 (C) 2017 Elsevier Ltd. 保留所有权利。
Postpartum depression affects approximately 15% of mothers. Unfortunately, treatment options for postpartum depression are limited. Pharmacological antidepressants such as fluoxetine (FLX) can be controversial due to inconclusive evidence of efficacy during the postpartum and concerns of neonatal exposure to antidepressants. Alternatively, non-pharmacological antidepressants such as exercise may be less controversial but its efficacy in postpartum depression is unclear. To investigate this, we treated rat dams daily with high levels of corticosterone (CORT; 40 mg/kg), to induce a depressive-like phenotype, or oil (vehicle for CORT) during the postpartum period. Within the oil and CORT conditions, four additional antidepressant conditions were created: 1. FLX (10 mg/kg) + exercise (voluntary access to running wheel); 2. FLX + no exercise; 3. Saline (vehicle for FLX) + exercise; 4. Saline + No exercise. We examined maternal care, depressive-like and anxiety-like behavior, stress reactivity; and hippocampal neurogenesis and dams were categorized as "high running" or "low running." FLX treatment, alone or with high running, prevented CORT-induced disruptions in maternal care. As expected, CORT increased depressive like behavior but exercise, regardless of running amount, reduced depressive-like behavior. Intriguingly, FLX, but not CORT, increased anxiety-like behavior, which was not mitigated by concurrent exercise. FLX treatment slightly but significantly facilitated serum CORT recovery after forced swim stress. CORT and FLX alone reduced neurogenesis, while exercise coupled with FLX increased density of doublecortin-expressing cells. High running increased density of doublecortin-expressing cells (immature neurons) in comparison to controls. Collectively, these findings indicate that FLX and exercise reverse different endophenotypes of depression in dams, which has translational implications for surveying treatment options of postpartum depression. (C) 2017 Elsevier Ltd. All rights reserved.