Steroid Catecholamine Interactions and Behavior

描述(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，这些神经递质与性二态大脑结构有关，这些结构介导了一种自然发生的动机行为--男性性行为的激活。在这里研究的动物模型系统日本鹌鹑中，睾酮能够激活雄性的动机和表现成分-成年雄性的典型生殖行为，但不能激活成年雌性的所有方面的行为。在胚胎发育过程中控制这种性别差异分化的内分泌机制对睾酮的反应已被理解。成年期的这种荷尔蒙激活需要通过视前内侧核中的芳香酶将睾酮代谢成17β雌二醇，这是一个大脑区域，男性的体积大于女性。以前的研究已经证实，雌二醇对行为的作用既有慢的方式(几小时到几天)，也有快的方式(几秒到几分钟)，芳香酶也同样以这种双峰方式调节。在当前的应用中，提出了组织成5个目标的14个实验。目的研究男性和女性在控制男性典型行为的神经回路中的差异，这可能解释了睾酮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视前内侧核中与控制男性典型行为的动机和表现成分有关的功能拓扑图，比较控制这两个方面行为的机制将使我们能够识别特定于动机控制的神经内分泌机制。在AIM II中，将利用即刻早期基因方法对调节这一男性典型动机行为的性二型回路进行功能分析，确定立即早期基因诱导的原因并评估其功能。在目标III中，将评估与行为产生有关的儿茶酚胺向上投射到视前内侧核的地形变化和这些细胞组中的基因表达，这些细胞群以前曾被认为与动机行为的控制有关。目的IV涉及体内芳香酶活性快速变化的调节机制，目的V涉及介导雌激素对行为的快速影响的受体系统和脑区的研究。这些关于神经内分泌控制性动机的研究为了解类固醇激素对性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。这类研究对于开发旨在解决与心理健康相关的行为病理的治疗方法的科学基础至关重要。对动机行为中类固醇激素激活的性别差异的研究也可以提供对性分化和/或激素调节的精神疾病的病因的洞察。各种各样的神经和精神综合征，可能与单胺能神经传递不平衡有关，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分化或类固醇依赖型疾病的病因提供洞察力。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所介导的。

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.