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Activation of orexin neurons in dorsomedial/perifornical hypothalamus and antidepressant reversal in a rodent model of depression.

Nollet, M, Gaillard, P, Minier, F, Tanti, A, Belzung, C and Leman, S (2011) Activation of orexin neurons in dorsomedial/perifornical hypothalamus and antidepressant reversal in a rodent model of depression. Neuropharmacology, 61 (1-2). pp. 336-346.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Gaillard, P
Minier, F
Tanti, A
Belzung, C
Leman, S
Date : July 2011
DOI : 10.1016/j.neuropharm.2011.04.022
Uncontrolled Keywords : Animals, Antidepressive Agents, Depression, Disease Models, Animal, Dorsomedial Hypothalamic Nucleus, Hypothalamus, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Inbred BALB C, Neurons, Neuropeptides, Random Allocation
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 09:45
Last Modified : 24 Jan 2020 17:36

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