Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7224, 9 quai St Bernard, Paris CEDEX 05, France.
Gen Comp Endocrinol. 2013 Jul 1;188:218-25. doi: 10.1016/j.ygcen.2013.03.031. Epub 2013 Apr 10.
In the present study, we investigated the role of the androgen receptor (AR) in the nervous system in the regulation of aggressive behavior and arginine vasopressin and galanin systems by testosterone. For this purpose, we used a conditional mouse line selectively lacking AR gene in the nervous system, backcrossed onto the C57BL/6J strain. Adult males were gonadectomized and supplemented with similar amounts of testosterone. When tested on two consecutive days in the resident intruder paradigm, fewer males of the mutant group exhibited aggressive behavior compared to their control littermates. In addition, a high latency to the first offensive attack was observed for the few animals that exhibited fighting behavior. This alteration was associated with a normal anogenital chemoinvestigation of intruder males. In olfactory discrimination tasks, sexual experience enhanced preference towards female-soiled bedding rather than male-soiled bedding and estrus females rather than intact males, regardless of genotype. This indicated that the behavioral alteration induced by neural AR mutation occurs in brain areas located downstream from the olfactory bulb. Quantification of the sexually dimorphic cell populations expressing preprovasopressin and galanin mRNAs in the bed nucleus of stria terminalis (BNST) and vasopressin-neurophysin 2 and galanin immunoreactivity in the lateral septum showed no significant differences between the two genotypes. The present findings indicate that the neural AR is required in the expression of aggressive behavior but not in the sexual differentiation of AVP and galanin cell number in the BNST and fiber immunoreactivity in the lateral septum. They also suggest that AR in the nervous system could mediate activational effects of testosterone in the regulation of aggressive behavior during adulthood.
在本研究中,我们研究了雄激素受体 (AR) 在神经系统中对睾酮调节攻击性行为和精氨酸加压素 (AVP) 和甘丙肽系统的作用。为此,我们使用了一种条件性小鼠系,该小鼠系在神经系统中选择性缺失 AR 基因,并与 C57BL/6J 品系进行了回交。成年雄性小鼠被去势并补充了等量的睾酮。在连续两天的常驻入侵者范式中进行测试时,与对照组相比,突变组的雄性表现出的攻击性行为较少。此外,观察到表现出攻击性行为的少数动物的第一次进攻潜伏期很高。这种改变与入侵者雄性的正常肛门生殖器化学探测有关。在嗅觉辨别任务中,无论基因型如何,性经验都会增强对雌性污染垫而非雄性污染垫以及发情雌性而非完整雄性的偏好。这表明,由神经 AR 突变引起的行为改变发生在嗅球下游的脑区。在终纹床核 (BNST) 中表达前加压素和甘丙肽 mRNA 的性二态细胞群体以及外侧隔室中的血管加压素神经肽 2 和甘丙肽免疫反应性的定量分析显示,两种基因型之间没有显著差异。本研究结果表明,神经 AR 是表达攻击性行为所必需的,但不是 BNST 中 AVP 和甘丙肽细胞数量以及外侧隔纤维免疫反应性的性分化所必需的。它们还表明,神经系统中的 AR 可以介导睾酮在成年期调节攻击性行为中的激活作用。