PROLACTIN EFFECTS ON BEHAVIOR: SITES AND MODES OF ACTION

描述(申请人提供)：这项研究的长期目标是扩大我们对潜在的社会互动的神经内分泌机制的理解。父母与幼崽的互动是社会行为体系中特别重要的组成部分，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，涉及父母养育的神经回路是否与其他社会行为相同的问题仍有待解决。这些研究探讨了催乳素(PRL)在协调各种行为和神经内分泌变化方面的整合作用的神经机制，这些变化是成功的父母照料所必需的。环鸽(Streptopelia Risoria)被选为研究的模式物种，因为它拥有异常丰富的依赖催乳素的行为和生理变化，支持育儿。该项目有四个具体目标：1)使用即时早期基因产物的免疫细胞化学图谱来确定PRL、社会线索和经验因素是否影响构成父母动机和父母行为表达的神经元回路的活动；2)确定大脑中的PRL信号是否受到以前的育儿经验和与育儿相关的生理状态的调节(使用实时荧光聚合酶链式反应、原位杂交和免疫细胞化学来测量PRL受体的表达和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对性腺活动的抑制作用中的作用，这可能是显示其他PRL诱导的亲代反应性变化所必需的(使用实时荧光聚合酶链式反应、原位杂交和免疫细胞化学来测量特定脑区的表达)；4)确定脑中PRL信号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下调鸽子脑中PRL受体的表达)。这些研究将扩大我们对社会性背后的神经机制的理解，并可能导致更好地诊断和治疗处于社会适应障碍风险中的个人。它们还可能揭示PRL分泌升高的哺乳妇女和患有PRL分泌脑瘤的男性和女性不孕不育的原因。

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.