Long-term voluntary exercise and the mouse hypothalamic-pituitary-adrenocortical axis: Impact of concurrent treatment with the antidepressant drug tianeptine
Long-term voluntary exercise and the mouse hypothalamic-pituitary-adrenocortical axis: Impact of concurrent treatment with the antidepressant drug tianeptine
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DOI：
10.1111/j.1365-2826.2006.01489.x
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发表时间：
2006-12-01
影响因子：
3.2
通讯作者：
Reul, J. M. H. M.
中科院分区：
文献类型：
--
作者：
Droste, S. K.;Schweizer, M. C.;Reul, J. M. H. M.
我们研究了自愿运动和抗抑郁药治疗（噻奈普汀; 20 mg/kg/天; 4周）是否对小鼠下丘脑-垂体-肾上腺皮质（HPA）轴产生协同作用。动物可以使用转轮，用抗抑郁药治疗，或同时接受两种条件。对照组小鼠不接受跑步轮和药物治疗。运动导致肾上腺的不对称变化。然而，久坐的老鼠左肾上腺比右肾上腺大，这种情况在运动的动物中被消除，主要是由于右肾上腺皮质的扩大。然而，抗抑郁药单独治疗是无效的，而抗抑郁药治疗和运动的组合导致两个肾上腺皮质的扩大。在这些各自的条件下，酪氨酸羟化酶（TH）mRNA的表达水平在左，右肾上腺髓质变化很大，平行于肾上腺皮质大小的变化。运动小鼠蓝斑TH mRNA表达显著增加，与噻奈普汀治疗无关。自愿运动后下丘脑室旁核促肾上腺皮质激素释放因子mRNA水平下降，但不受噻奈普汀。运动，特别是与噻奈普汀治疗相结合，导致清晨皮质酮基线血浆水平下降。如果动物暴露于新奇事物（即轻度心理应激源），则在运动小鼠中观察到血浆皮质酮水平的反应降低。相比之下，约束后，一个混合的身体和心理的应激源，运动小鼠显示出增强的血浆皮质酮的反应相比，控制;这是一个反应，甚至进一步加强在运动小鼠伴随治疗噻奈普汀。在任何一种情况下，血浆促肾上腺皮质激素水平组间无差异。因此，自主运动对HPA轴的调节有很大影响。同时噻奈普汀治疗导致协同作用，主要在肾上腺水平，影响其结构和功能。
We investigated whether voluntary exercise and concurrent antidepressant treatment (tianeptine; 20 mg/kg/day; 4 weeks) exert synergistic effects on the mouse hypothalamic-pituitary-adrenocortical (HPA) axis. Animals had access to a running wheel, were treated with the antidepressant, or received both conditions combined. Control mice received no running wheel and no drug treatment. Exercise resulted in asymmetric changes in the adrenal glands. Whereas sedentary mice had larger left adrenals than right ones, this situation was abolished in exercising animals, mainly due to enlargement of the right adrenal cortex. However, antidepressant treatment alone was ineffective whereas the combination of antidepressant treatment and exercise resulted in an enlargement of both adrenal cortices. In these respective conditions, the levels of tyrosine hydroxylase (TH) mRNA expression in the left and right adrenal medullas varied greatly in parallel to the changes observed in the adrenal cortex sizes. TH mRNA expression in the locus coeruleus of exercising mice was significantly increased irrespective of concomitant tianeptine treatment. Corticotrophin-releasing factor mRNA levels in the hypothalamic paraventricular nucleus were decreased after voluntary exercise but were unaffected by tianeptine. Exercise, particularly in combination with tianeptine treatment, resulted in decreased early morning baseline plasma levels of corticosterone. If animals were exposed to novelty (i.e. a mild psychological stressor), a decreased response in plasma corticosterone levels was observed in the exercising mice. By contrast, after restraint, a mixed physical and psychological stressor, exercising mice showed an enhanced response in plasma corticosterone compared to the controls; a response which was even further boosted in exercising mice concomitantly treated with tianeptine. Under either condition, plasma adrenocorticotrophic hormone levels were not different between groups. Thus, voluntary exercise impacts substantially on HPA axis regulation. Concurrent tianeptine treatment results in synergistic actions, mainly at the adrenal level, affecting both its structure and function.