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，涉及两性二态脑结构介导自然发生的动机行为，即男性性行为的激活。在日本鹌鹑（本文研究的动物模型系统）中，睾酮能够激活成年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的所有行为。胚胎发育过程中发生的内分泌机制控制了对睾酮反应的性别差异分化。这种激素在成年期的激活需要通过视前内侧核的芳香化酶将睾酮代谢为17 -雌二醇，视前内侧核是男性比女性体积更大的大脑区域。先前的研究已经证实雌二醇对行为的作用既有缓慢的（几小时到几天），也有快速的（几秒到几分钟），芳香化酶也同样以这种双峰方式受到调节。在目前的应用中，提出了14个实验，分为5个目标。目的1关注男性/女性在控制男性典型行为的神经回路上的差异，这可能解释了睾丸激素激活行为能力的显著性别差异。我们将在男性和女性中研究与男性典型行为的动机和表现成分控制相关的视前内侧核的功能地形，并比较控制这两个方面行为的机制，从而使我们能够确定特定于动机控制的神经内分泌机制。在Aim II中，将利用即时早期基因方法对调节这种男性典型动机行为的两性二态电路进行功能分析，确定即时早期基因诱导的原因并评估其功能。在目标III中，上升儿茶酚胺投射到视前内侧核的地形变化和这些细胞群中的基因表达，之前已经涉及动机行为的控制，将评估与行为产生有关的变化。目的IV涉及体内调节芳香酶活性快速变化的机制，目的V涉及受体系统和脑区介导雌激素对行为的快速影响的研究。这些关于性动机的神经内分泌控制的研究为理解类固醇激素对性动机行为控制的性别和性别差异的影响提供了一种分析方法。这样的研究对于为治疗与心理健康相关的行为病理学提供科学基础至关重要。对类固醇激素激活动机行为的性别差异的研究也可以为性别分化和/或激素调节的精神疾病的病因学提供见解。各种各样的神经和精神综合征，可能与单胺能神经传递的不平衡有关，在男性中更常见，或者在女性中更常见，这表明性类固醇激素分泌和作用的性别差异可能参与了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为性别分化或类固醇依赖性疾病的病因学提供见解。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.