Membrane androgen receptors may mediate androgen reinforcement.
Membrane androgen receptors may mediate androgen reinforcement.
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膜雄激素受体可能介导雄激素强化。
DOI：
10.1016/j.psyneuen.2010.01.007
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发表时间：
2010-08
影响因子：
3.7
通讯作者：
Wood, Ruth I.
中科院分区：
文献类型：
--
作者：
Sato, Satoru M.;Johansen, Jamie A.;Jordan, Cynthia L.;Wood, Ruth I.
关键词：
合成代谢类雄激素(AAS)滥用很普遍。此外，AAS正在加强，正如啮齿动物的自我给药所表明的那样。然而，转导AAS增强效应的受体尚不清楚。AAS可能与经典的核雄激素受体(AR)或膜受体结合。我们使用了两种方法来研究核受体在AAS自我管理中的作用。首先，我们在带有睾丸女性化突变(TFM)的大鼠身上测试了雄激素自我给药，这种突变干扰了雄激素结合。如果核受体对于AAS的自我管理是必不可少的，TFM男性就不应该自我管理雄激素。TFM雄性和野生型(WT)产仔仔以固定比例(FR)自我注射非芳香化雄激素双氢睾酮(DHT)或脑室内注射(ICV)，计划最高可达FR5。TFM和WT大鼠在DHT自身给药过程中均获得了对主动拨鼻的偏爱(TFM为66.4±9.6次/4h，WT为79.2±11.5次/4h)，并且随着FR要求的增加，拨鼻量增加。自主给药组大鼠的偏爱分数显著降低(TFM为42.3±5.3次/4h，WT为19.1±4.0次/4h)。我们还测试了在C3和C17连接到牛血清白蛋白(BSA)的DHT的自身给药，这仅限于在细胞表面的作用。在FR1，仓鼠被允许自我给予DHT、BSA和DHT-BSA结合物15天。仓鼠对DHT(18.0±4.1次/4h)和DHT-BSA结合物(10.0±3.7次/4h和21.0±7.2次/4h)表现出明显的偏好，而对BSA(2.5±2.4次/4h)没有明显的偏好。综上所述，这些数据表明，雄激素自我给药不需要核受体。此外，雄激素的自我给药可能是由质膜受体介导的。
Anabolic androgenic steroid (AAS) abuse is widespread. Moreover, AAS are reinforcing, as shown by self-administration in rodents. However, the receptors that transduce the reinforcing effects of AAS are unclear. AAS may bind to classical nuclear androgen receptors (AR) or membrane receptors. We used two approaches to examine the role of nuclear ARs in AAS self-administration. First, we tested androgen self-administration in rats with the testicular feminization mutation (Tfm), which interferes with androgen binding. If nuclear ARs are essential for AAS self-administration, Tfm males should not self-administer androgens. Tfm males and wild-type (WT) littermates self-administered the non-aromatizable androgen dihydrotestosterone (DHT) or vehicle intracerebroventricularly (ICV) at fixed ratio (FR) schedules up to FR5. Both Tfm and WT rats acquired a preference for the active nose-poke during DHT self-administration (66.4±9.6 responses/4h for Tfm and 79.2±11.5 for WT responses/4h), and nose-pokes increased as the FR requirement increased. Preference scores were significantly lower in rats self-administering vehicle (42.3±5.3 responses/4h for Tfm and 19.1±4.0 responses/4h for WT). We also tested self-administration of DHT conjugated to bovine serum albumin (BSA) at C3 and C17, which is limited to actions at the cell surface. Hamsters were allowed to self-administer DHT, BSA and DHT-BSA conjugates for 15 days at FR1. The hamsters showed a significant preference for DHT (18.0±4.1 responses/4h) or DHT-BSA conjugates (10.0±3.7 responses/4h and 21.0±7.2 responses/4h), but not for BSA (2.5±2.4 responses/4h). Taken together, these data demonstrate that nuclear ARs are not required for androgen self-administration. Furthermore, androgen self-administration may be mediated by plasma membrane receptors.
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