Steroid Catecholamine Interactions and Behavior

描述（由申请人提供）：本提案涉及类固醇激素和儿茶酚胺神经递质之间的相互关系，这些激素和神经递质与介导自然发生的动机行为（男性性行为）激活的性二态脑结构有关。在日本鹌鹑，这里研究的动物模型系统中，睾酮能够激活成年雄性的雄性典型生殖行为的动机和表现成分，但不能激活成年雌性行为的所有方面。在胚胎发育过程中发生的内分泌机制，控制这种性别差异的分化，以响应睾酮的理解。成年期的这种激素激活需要通过视前内侧核中的芳香化酶将睾酮代谢为17 β雌二醇，视前内侧核是一个大脑区域，男性的体积比女性大。以前的工作已经确定，雌二醇以缓慢的方式（数小时至数天）以及快速的方式（数秒至数分钟）对行为起作用，芳香酶以这种双峰方式进行类似的调节。在本申请中，提出了组织成5个目标的14个实验。目的我关注的男性/女性的差异，在控制男性典型的行为，可能会解释显着的性别差异的睾酮激活行为的能力的神经回路。一个先前确定的功能地形在视前内侧核有关的男性典型的行为的动机和性能组件的控制将在男性和女性的研究和控制这两个方面的行为的机制的比较，将使我们能够识别特定的神经内分泌机制的动机控制。在目的II中，立即早期基因的方法将被用来功能分析的性二态性电路调节这种男性典型的动机行为，确定立即早期基因诱导的原因，并评估其功能。在目标III中，地形变化上升的儿茶酚胺预测视前内侧核和基因表达在这些细胞群中，以前已经牵连在动机行为的控制，将评估有关的行为生产。目的IV涉及调节体内芳香化酶活性快速变化的机制，目的V涉及调节雌激素对行为快速影响的受体系统和脑区的研究。这些关于性动机的神经内分泌控制的研究为了解类固醇激素对性别的影响以及在控制动机行为方面的性别差异提供了一种分析方法。这些研究对于开发旨在解决与心理健康相关的行为病理学的治疗方法的科学基础至关重要。对类固醇激素激活动机行为的性别差异的研究也可以深入了解性分化和/或激素调节的精神疾病的病因。各种各样的神经和精神综合征，可能与单胺能神经传递失衡有关，在男性中更常见，或在女性中更常见，这表明性类固醇激素的分泌和作用的性别差异可能参与这些综合征的发展和/或维持。类固醇激素-神经递质相互作用的研究可以提供深入了解性分化或类固醇依赖性疾病的病因。类固醇激素功能的改变可能对人类情感和性动机行为的控制产生重大影响，这些影响很可能是由类固醇诱导的神经传递改变介导的。

DESCRIPTION (provided by applicant): This proposal concerns interrelationships among steroid hormones and catecholamine neurotransmitters in relation to sexually dimorphic brain structures mediating the activation of a naturally occurring motivated behavior, male sexual behavior. In Japanese quail, the animal model system investigated here, testosterone is able to activate both motivational and performance components of male-typical reproductive behaviors in adult males but does not activate all aspects of the behavior in adult females. The endocrine mechanisms occurring during embryonic development that control the differentiation of this sex difference in response to testosterone are understood. This hormonal activation in adulthood requires the metabolism of testosterone to 17beta estradiol by the enzyme aromatase in the preoptic medial nucleus, a brain area that is larger in volume in males than in females. Previous work has established that estradiol acts on behavior both in a slow manner (hours to days) as well as in a fast manner (seconds to minutes) and aromatase is similarly regulated in this bimodal fashion. In the current application 14 experiments organized into 5 aims are proposed. Aim I concerns male/female differences in the neural circuit controlling male-typical behaviors that might explain the remarkable sex difference in the ability of testosterone to activate behavior. A previously identified functional topography in the preoptic medial nucleus related to the control of motivational and performance components of male-typical behavior will be studied in both males and females and a comparison of the mechanisms controlling these two aspects of the behavior will allow us to identify neuroendocrine mechanisms specific to motivational control. In Aim II, immediate early gene methods will be utilized to functionally analyze the sexually dimorphic circuit regulating this male-typical motivated behavior, identify the causes of the immediate early gene induction and assess its function. In aim III, topographic variation in ascending catecholamine projections to the preoptic medial nucleus and gene expression in these cell groups, that have been previously implicated in the control of motivated behaviors, will be assessed in relation to behavioral production. Aim IV concerns the mechanisms regulating rapid changes in the activity of aromatase in vivo and Aim V involves studies of the receptor systems and brain areas mediating the rapid effects of estrogen on behavior. These studies on the neuroendocrine control of sexual motivation provide an assay for understanding the effects of steroid hormones on sex and gender differences in the control of motivated behaviors. Such studies are essential for the development of a scientific underpinning for treatments designed to address behavioral pathologies connected to mental health. Investigations of sex differences in steroid hormone activation of motivated behaviors can also provide insight into the etiology of sexually differentiated and/or hormone- regulated psychiatric diseases. A wide variety of neurological and psychiatric syndromes, likely related to imbalances in monoaminergic neurotransmission, are more common in males, or are more common in females, suggesting that sex differences in the secretion and action of sex steroid hormones may be involved in the development and/or maintenance of these syndromes. The study of steroid hormone-neurotransmitter interactions can provide insight into the etiology of sexually differentiated or steroid-dependent diseases. Alteration in steroid hormone functioning may have major consequences on the control of affective and sexual motivated behaviors in humans and these effects are in all probability mediated by the steroid-induced alterations of neurotransmission.