Testosterone's metabolism in the hippocampus may mediate its anti-anxiety effects in male rats
Testosterone's metabolism in the hippocampus may mediate its anti-anxiety effects in male rats
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DOI：
10.1016/j.pbb.2004.04.019
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Edinger, KL
中科院分区：
文献类型：
--
作者：
Frye, CA;Edinger, KL
雄激素可能介导焦虑行为;然而，雄激素的这些作用和机制还不清楚。以下实验研究了睾酮（T）对焦虑行为的影响是否由其5 α-还原的非芳香化代谢物二氢睾酮（DHT）和/或其3 α-羟基类固醇脱氢酶（3 α-HSD）还原的代谢物3 α-雄甾烷酮（3 α-二醇）介导。在实验1中，性腺完整的成年雄性大鼠和性腺切除（GDX），DHT替代大鼠具有类似的低水平的焦虑行为在开放领域和升高十字迷宫和恐惧行为在防御冻结任务与GDX对照组大鼠相比。在实验2中，在海马体中植入空白插入物的完整或DHT替代大鼠比在背侧海马体中植入消炎痛（一种3 α-HSD抑制剂）的大鼠表现出更少的焦虑行为。这些数据表明，T的5 α-还原代谢物，DHT，可以减少焦虑行为，阻断海马体中3 α-二醇的代谢可以减弱这些作用。(C)2004年爱思唯尔公司All rights reserved.
Androgens may mediate anxiety behaviors; however, these effects and mechanisms of androgens are not well understood. The following experiments investigated whether testosterone (T)'s effects on anxiety behavior are mediated by its 5alpha-reduced, nonaromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha-androstanediol (3alpha-diol). In Experiment 1, gonadally-intact adult male rats and gonadectomized (GDX), DHT-replaced rats had similar low levels of anxiety behavior in the open field and elevated plus maze and fear behavior in the defensive freezing task compared with GDX control rats. In Experiment 2, intact or DHT-replaced rats that received blank inserts to the hippocampus demonstrated less anxiety behavior than did rats administered an implant of indomethacin, a 3alpha-HSD inhibitor, to the dorsal hippocampus. These data indicate that T's 5alpha-reduced metabolite, DHT, can reduce anxiety behavior and that blocking metabolism to 3alpha-diol in the hippocampus can attenuate these effects. (C) 2004 Elsevier Inc. All rights reserved.