Antidepressant-like effects of the glucocorticoid receptor antagonist RU-43044 are associated with changes in prefrontal dopamine in mouse models of depression

被引：88

作者：

Ago, Yukio ^{[1
]}

Arikawa, Shinsuke ^{[1
]}

Yata, Miyuki ^{[1
]}

Yano, Koji ^{[1
]}

Abe, Michikazu ^{[2
]}

Takuma, Kazuhiro ^{[1
]}

Matsuda, Toshio ^{[1
,3
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Med Pharmacol, Suita, Osaka 5650871, Japan

[2] Mitsubishi Tanabe Pharma Corp, Div Res, Pharmacol Lab, Aoba Ku, Kanagawa 2270033, Japan

[3] Osaka Univ, Grad Sch Med, Osaka Hamamatsu Joint Res Ctr Child Mental Dev, Dept Expt Dis Model, Suita, Osaka 5650871, Japan

来源：

NEUROPHARMACOLOGY | 2008年 / 55卷 / 08期

关键词：

Glucocorticoid receptor antagonist; Antidepressant; Dopamine; Prefrontal cortex; Isolation rearing; Corticosterone;

D O I：

10.1016/j.neuropharm.2008.08.026

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Chronic corticosterone and isolation rearing paradigms may provide reliable mouse models of depression. Using these models, the present study examined if the specific glucocorticoid receptor antagonist, RU-43044, has an antidepressant-like effect, and Studied the possible role of prefrontal neurotransmission on the behavioral effects. Chronic administration of corticosterone and isolation rearing increased the immobility time in the forced swim and tail suspension tests. Subchronic treatment with RU-43044 decreased the immobility time in the forced swim test in chronic corticosterone-treated and isolation-reared mice, but not the control mice. Chronic corticosterone decreased the levels of cortical glucocorticoid receptors and stress-induced increases in plasma corticosterone levels, and blocked the response of plasma corticosterone to dexamethasone, while isolation rearing did not cause any changes in the glucocorticoid receptor system. Both chronic corticosterone and isolation rearing markedly increased high K+-induced dopamine release, but not serotonin release, in the prefrontal cortex. Subchronic RU-43044 reversed the enhanced release of dopamine in the prefrontal cortex of chronic corticosterone-treated and isolation-reared mice. These results Suggest that chronic corticosterone and isolation rearing increase the depressive-like behavior in glucocorticoid receptor-dependent and independent manners, respectively, and that RU-43044 shows an antidepressant-like effect, probably via an inhibition of enhanced prefrontal dopaminergic neurotransmission in these mouse models. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1355 / 1363

页数：9

共 73 条

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