PROLACTIN EFFECTS ON BEHAVIOR: SITES AND MODES OF ACTION

描述（由申请人提供）：这项研究的长期目标是扩大我们对社会互动背后的神经内分泌机制的理解。父母与孩子的互动是社会行为的重要组成部分，因为它们对生存至关重要。然而，这些相互作用背后的神经和激素机制还没有得到充分的描述，以及参与育儿的神经回路是否与其他社会行为相同的问题仍有待解决。拟议的研究探讨了负责催乳素（PRL）在协调成功的父母照顾所必需的各种行为和神经内分泌变化的综合行动的神经机制。环鸽（Streptopelia risoria）被选为调查的模式物种，因为它有一个异常丰富的剧目PRL依赖的行为和生理变化，支持养育。该项目有四个具体目标：1）使用免疫细胞化学作图的即时早期基因产物，以确定是否催乳素，社会线索，和经验因素的影响，在神经元回路的活动，父母的动机和父母的行为表达的基础; 2）确定大脑中的PRL信号是否受到先前育儿经验和与育儿相关的生理状态的调节（使用真实的时间PCR、原位杂交和免疫细胞化学来测量PRL受体表达和PRL敏感信号分子的核转位）; 3）探讨促性腺激素释放激素（GnRH）和促性腺激素抑制激素（GnlH）在介导PRL抑制性腺活动中的作用。这可能是必要的，以便显示其他PRL诱导的亲代反应性变化（使用真实的时间PCR、原位杂交和免疫细胞化学来测量特定脑区域中的表达）; 4）确定脑中PRL信号传导在促进亲代行为和性腺轴抑制中的功能重要性（使用反义寡核苷酸技术敲低鸽子脑中PRL受体表达）。这些研究将扩大我们对社会性背后的神经机制的理解，并可能导致更好的诊断和治疗有社会适应障碍风险的个体。他们也可能阐明泌乳素分泌升高的哺乳期妇女和泌乳素分泌垂体瘤的男性和女性不孕的原因。

DESCRIPTION (provided by applicant): The long-term goal of this research is to expand our understanding of the neuroendocrine mechanisms underlying social interactions. Parental interactions with young are particularly important components of the social behavior repertoire because they are critical for survival. However, the neural and hormonal mechanisms underlying these interactions have not been adequately described and the question of whether the neural circuitry involved in parenting is common to other social behaviors remains to be resolved. The proposed studies explore the neural mechanisms responsible for the integrative actions of prolactin (PRL) in coordinating the diverse behavioral and neuroendocrine changes that are necessary for successful parental care. The ring dove (Streptopelia risoria) is chosen as the model species for investigation because it has an unusually rich repertoire of PRL-dependent behavioral and physiological changes that support parenting. The project has four specific aims: 1) to use immunocytochemical mapping of immediate early gene products to determine if PRL, social cues, and experiential factors influence activity in neuronal circuits that underlie parental motivation and parental behavior expression; 2) to determine if PRL signaling in the brain is modulated by previous parenting experience and during physiological states associated with parenting (using real time PCR, in situ hybridization, and immunocytochemistry to measure PRL receptor expression and nuclear translocation of PRL-sensitive signaling molecules); 3) to explore the role of gonadotropin releasing hormone (GnRH) and gonadotropin inhibiting hormone (GnlH) in mediating PRL's suppressive action on gonadal activity, which may be necessary in order for other PRL-induced changes in parental responsiveness to be displayed (using real time PCR, in situ hybridization, and immunocytochemistry to measure expression in specific brain regions); 4) to determine the functional importance of PRL signaling in the brain in promoting parental behavior and gonadal axis suppression (using antisense oligonucleotide technology to knock down PRL receptor expression in dove brain). These studies will expand our understanding of neural mechanisms underlying sociality and could lead to better diagnosis and treatment of individuals at risk for social adjustment disorders. They may also shed light on the causes of infertility in nursing women with elevated PRL secretion and in men and women with PRL-secreting pituitary tumors.