增食欲素
内分泌学
内科学
下丘脑
氟西汀
抗抑郁药
黑色素浓缩激素
食欲素受体
外侧下丘脑
行为绝望测验
食欲素-A
神经肽
化学
血清素
受体
海马体
医学
作者
Mathieu Nollet,Philippe Gaillard,Frédéric Minier,Arnaud Tanti,Catherine Belzung,Samuel Leman
标识
DOI:10.1016/j.neuropharm.2011.04.022
摘要
Chronic stressful life events are risk factors for depression often accompanied by homeostatic disturbances. Hypothalamic neuropeptides, such as orexins (OXs) and melanin-concentrating hormone (MCH), are involved in regulation of several autonomic functions that are altered in depression. However, little is known about the link between orexinergic or MCH-ergic systems and depression. Using double immunohistochemical labeling for OX- or MCH-containing neurons and Fos protein, we studied the effects of a chronic selective serotonin reuptake inhibitor antidepressant treatment (fluoxetine) on the OX and MCH neuronal activation in mice exposed to unpredictable chronic mild stress (UCMS), a rodent model of depression. Western blot was also performed to assess OX and MCH receptor expression in various brain areas. Finally, almorexant, a dual OX receptor antagonist, was assessed in the tail suspension test. UCMS induced physical and behavioral disturbances in mice reversed by 6-week fluoxetine treatment. Orexinergic neurons were more activated in the dorsomedial and perifornical hypothalamic area (DMH-PFA) of UCMS-subjected mice compared to the lateral hypothalamus (LH), and this increase was reversed by 6-week fluoxetine treatment. UCMS also reduced expression of OX-receptor 2 in the thalamus and hypothalamus, but not in animals chronically treated with fluoxetine. MCH neurons were neither affected by UCMS nor by antidepressant treatment, while UCMS modulated MCH receptor 1 expression in thalamus and hippocampus. Finally, chronic but not acute administration of almorexant, induced antidepressant-like effect in the tail suspension test. These data suggest that OX neurons in the DMH-PFA and MCH-ergic system may contribute to the pathophysiology of depressive disorders.
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