Anabolic androgenic steroids and forebrain GABAergic transmission.
Anabolic androgenic steroids and forebrain GABAergic transmission.
复制标题
合成代谢雄激素类固醇和前脑 GABA 能传输。
DOI：
10.1016/j.neuroscience.2005.08.039
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Clark,AS
中科院分区：
文献类型：
--
作者：
Henderson,LP;Penatti,CAA;Jones,BL;Yang,P;Clark,AS
合成代谢雄激素类固醇是睾酮的合成衍生物，设计用于治疗目的，但现在主要用作滥用药物。与使用合成代谢雄激素类固醇相关的最常见的行为影响是焦虑、攻击性和生殖行为的改变，包括青春期的开始和性接受能力的改变。前脑gaba能回路是这些行为的基础，并受性腺类固醇调节。我们实验室的研究表明，gaba受体在大鼠和小鼠前脑中的表达和功能因性别和发情周期而异。我们还发现，gaba受体的表达在青春期到成年的过程中发生了显著的变化。由于gaba能系统既对类固醇敏感，又对使用合成代谢雄激素改变行为的表达至关重要，因此前脑gaba受体是评估合成代谢雄激素分子作用如何转化为已知行为结果的有吸引力的候选者。我们的研究表明，合成代谢雄激素类固醇可引起gaba受体介导电流的急性调节，以及gaba受体表达和前脑gaba能传递的慢性调节。由于合成代谢雄激素类固醇的使用现在不仅在青春期男孩中很普遍，而且在越来越多的青春期女孩中也很普遍，我们也对确定合成代谢雄激素类固醇的年龄和性别特异性作用特别感兴趣。我们的数据显示，慢性合成代谢雄激素类固醇暴露对青春期动物的影响可能比成年动物更大，雌性动物比雄性动物更明显。这些数据对我们所做的研究具有特别重要的意义，这些研究表明，慢性合成代谢雄激素类固醇暴露会改变青春期的开始、发情周期和性接受性。
Anabolic androgenic steroids are synthetic derivatives of testosterone designed for therapeutic purposes, but now taken predominantly as drugs of abuse. The most common behavioral effects associated with anabolic androgenic steroid use are changes in anxiety, aggression and reproductive behaviors, including the onset of puberty and sexual receptivity. GABAergic circuits in the forebrain underlie these behaviors and are regulated by gonadal steroids. Work from our laboratories has shown that the expression and function of GABAAreceptors in the rat and mouse forebrain varies between the sexes and across the estrous cycle. We have also shown that there are significant changes in GABAAreceptor expression that occur with the progression through puberty to adulthood. Because GABAergic systems are both steroid-sensitive and critical for the expression of behaviors altered with anabolic androgenic steroid use, forebrain GABAAreceptors are an attractive candidate to assess how molecular actions of anabolic androgenic steroids may be translated to known behavioral outcomes. Our studies demonstrate that anabolic androgenic steroids elicit both acute modulation of GABAAreceptor-mediated currents, as well as chronic regulation of GABAAreceptor expression and forebrain GABAergic transmission. Because anabolic androgenic steroid use has now become prevalent not only among adolescent boys, but in an increasing number of adolescent girls, we have also been particularly interested in determining age- and sex-specific effects of anabolic androgenic steroids. Our data show that the effects of chronic anabolic androgenic steroid exposure can be greater for adolescent than adult animals and are more marked in females than in males. These data have particularly important implications with respect to studies we have done demonstrating that chronic anabolic androgenic steroid exposure alters the onset of puberty, estrous cyclicity and sexual receptivity.