Estrogen desensitizes 5-HT_1A receptors and reduces levels of G_z, G_i1 and G_i3 proteins in the hypothalamus

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• 作者：Raap ; Daní ; K. ; et. al.
• 关键词：Oxytocin ; ACTH ; Signaling ; G protein ; Serotonin ; Antidepressants
• 刊名：Neuropharmacology
• 出版年：2000
• 出版时间：September, 2000
• 年：2000
• 卷：39
• 期：10
• 页码：1823-1832
• 全文大小：275 K

文摘

The present study investigated whether estrogen would desensitize hypothalamic serotonin_1A (5-HT_1A) receptors by examining the neuroendocrine response to 8-OH-DPAT, a 5-HT_1A agonist. Rats were ovariectomized, allowed to recover for 5 days, then given 2 daily injections of estradiol benzoate or vehicle (10 μg/day, s.c.). Twenty-four hours after the second injection, rats were challenged with a sub-maximal dose of 8-OH-DPAT (50 μg/kg, sc) or saline 15 min prior to sacrifice. 8-OH-DPAT produced a significant increase in plasma oxytocin, ACTH and corticosterone levels in ovariectomized rats. While estrogen treatment for 2 days did not alter basal hormone levels, it did significantly reduce the magnitude of oxytocin, ACTH and corticosterone responses to 8-OH-DPAT. The reduction in hormone responses was accompanied by a significant reduction in hypothalamic levels of G_z, G_i1 and G_i3 proteins (by 50 % , 30 % and 50 % , respectively). These findings suggest that a reduction in these G proteins may contribute to the mechanisms underlying estrogen-induced desensitization of 5-HT_1A receptors. The desensitization of 5-HT_1A receptors has been suggested to underlie the therapeutic effects of antidepressant 5-HT uptake inhibitors (SSRIs). Thus, the present results suggest that estrogen or estrogen-like substances in combination with SSRIs may prove effective in developing novel therapeutic strategies for neuropsychiatric disorders in women. Publisher: Elsevier Science Language of Publication: English Item Identifier: S0028-3908(99)00264-6 Publication Type: Article ISSN: 0028-3908 Cited by:

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Footnotes:

1. Current address: Department of Psychology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.

2. Part of this review was presented at the Seventh International Congress of Biological Psychiatry in Berlin, Germany, 1-7 July 2001.