Steroid Catecholamine Interactions and Behavior

描述（由申请人提供）：社会互动的调节对于基础科学家和对精神疾病病因学感兴趣的临床医生都具有根本的重要性。 这些研究可以产生一般原则，有助于深入了解精神障碍的病因学和病理生理学。这一努力是NIMH和本研究计划的主要目标。社会行为的激活不仅涉及个体在适当的刺激存在下，而且还涉及处于适当的动机状态。类固醇激素睾酮是一种激素原，可以通过芳香酶代谢成雌激素，如雌二醇。在视前区，睾酮转化为雌二醇对于性动机和性表现的激活至关重要。Escherichia以两种模式起作用，一种是涉及与细胞内受体结合和诱导基因表达的慢模式，另一种是涉及与细胞膜相互作用和激活第二信使系统的快模式。我们最近的研究表明，脑芳香化酶产生的雌激素的快速作用对激活食欲性行为（动机方面）很重要，而较慢的基因组作用对激活交配性能很重要。除了视前区，芳香化酶还广泛分布于社会行为网络的脑核团中。目前的建议（目的一）的一个目标是调查在男性和女性的功能，雌激素的生产在其他核的社会行为网络，除了视前区和雌激素的影响，动机方面的其他社会行为，除了性行为。另一个目标（目标II）是研究类固醇激素对男性性动机的快速非基因组效应，以及这些效应是否特异于性动机或扩展到其他动机反应。我们还将评估这些影响的神经解剖靶点。目的III中的后续研究将解决这些效应的一些细胞机制。例如，有证据表明，嵌入细胞膜的雌激素受体与兴奋性氨基酸受体谷氨酸的受体相互作用。这种相互作用的解剖模式和它们在动机中所起的作用将被研究。最后，在最后一个目标（IV）中，将研究将雄激素转化为雌激素的酶芳香化酶的快速调节。我们将评估调节动机的行为情况如何也可能调节芳香化酶，从而影响与行为激活相关的特定大脑区域中雌二醇的含量。

DESCRIPTION (provided by applicant): The regulation of social interactions is of fundamental importance to both basic scientists and to clinicians interested in the etiology of mental illness. Such studies can produce general principles that will facilitate insights into the etiology and pathophysiology of mental disorders. This endeavor is a major goal of the NIMH and of this research program. The activation of social behaviors involves not only an individual being in the presence of an appropriate stimulus but also being in the appropriate motivational state. The steroid hormone testosterone is a pro-hormone that can be metabolized via the enzyme aromatase to an estrogen such as estradiol. In the preoptic area, the conversion of testosterone to estradiol is critical for the activation of both sexual motivation and performance. Estradiol ca act in two modes, a slow mode that involves binding to intracellular receptors and the induction of gene expression and a fast mode that involves interactions with the cell membrane and the activation of second messenger systems. Our recent work has shown that the fast actions of estrogens produced by brain aromatase are important for the activation of appetitive sexual behavior (motivational aspects) while the slower genomic actions are important for the activation of copulatory performance. In addition to the preoptic area, aromatase is widely distributed in brain nuclei of the social behavior network. One goal of the current proposal (Aim I) is to investigate in both males and females the function of estrogen production in other nuclei of the social behavior network besides the preoptic area and the effects of estrogens on motivational aspects of other social behaviors besides sexual behavior. Another goal (Aim II) is to study the rapid non-genomic effects of steroid hormones on male sexual motivation and whether these effects are specific to sexual motivation or extend to other motivated responses. We will also assess the neuroanatomical target sites of these effects. Subsequent studies in Aim III will address some the cellular mechanisms of these effects. For example, there is evidence that estrogen receptors embedded in the cell membrane interact with receptors for the excitatory amino acid receptor glutamate. The anatomical pattern of such interactions and the role they play in motivation will be investigated. Finally in the last aim (IV) the rapid regulation of the enzyme, aromatase, that converts androgens to estrogens will be studied. We will assess how behavioral situations that modulate motivation might also modulate aromatase that in turn will affect how much estradiol is available in specific brain areas related to behavioral activation.