Neuropeptide Involvement In Male Social Behavior

神经肽参与男性社会行为

• 批准号: 7545910
• 负责人: JAMES I KOENIG
• 金额: $ 22.71万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7545910
• 关键词: Address; Adolescence; Adult; Affect; Amino Acids; Amygdaloid structure; Anhedonia; Animal Model; Animals; Antipsychotic Agents; Area; Autistic Disorder; Behavior; Behavioral; Biological; Birth; Brain; Brain region; Cell Nucleus; Cells; Data; Defect; Delusions; Development; Disease; Drug effect disorder; Endocrine; Epidemiology; Exhibits; Family; Feeling; Female; Fiber; Functional disorder; Gene Expression; Genetic; Glucocorticoids; Hallucinations; Happiness; Human; Humanities; Hypothalamic structure; Individual; Laboratories; Lateral; Lateral Septal Nucleus; Left; Literature; Marketing; Maternal Behavior; Messenger RNA; Motivation; Nature; Neurons; Neuropeptides; Oxytocin; Oxytocin Receptor; Patients; Peptides; Pharmaceutical Preparations; Phenotype; Population; Precipitating Factors; Pregnancy; Preparation; Production; Puberty; Rattus; Role; Schizophrenia; Series; Site; Social Behavior; Social Functioning; Social Interaction; Societies; Speech; Stress; Structure of terminal stria nuclei of preoptic region; Symptoms; System; Testing; Time; Tissues; Translating; Vasopressins; base; human disease; mRNA Expression; male; novel; paraventricular nucleus; pre-clinical; prenatal stress; programs; receptor binding; social; supraoptic nucleus

DESCRIPTION (provided by applicant): Oxytocin (OT) and vasopressin production are concentrated in the hypothalamic paraventricular and supraoptic nuclei. Fibers emanating from these cells innervate limbic brain areas that are involved in the control of social behavior. Several human diseases, like schizophrenia and autism, have prominent social manifestations that adversely affect the individuals suffering from these diseases. Approximately one-third of schizophrenic patients are afflicted with the negative symptoms of schizophrenia (e.g. asociality, anhedonia, avolition of speech), which are not treated by the currently available antipsychotic medications. The biological basis of these symptoms is unknown. My laboratory has developed a novel animal model that exhibits many aspects of the schizophrenia phenotype including compromised social drive and function. In this application, we propose to use this animal preparation to investigate the etiopathophysiology of the social incompetence exhibited by these animals and its relationship to schizophrenia. Our preliminary data point to an alteration in the brain OT system as the precipitating factor for the social dysfunction of prenatally stressed male rats. Therefore, our overarching hypothesis is that prenatal stress exposure compromises the development of the brain OT neurons and the dysfunction of the oxytocinergic neurons generate the social dysfunction present in the prenatally stressed rats, and potentially in schizophrenic patients with negative symptoms. To test this hypothesis the following specific aims are proposed. Specific Aim 1. Examine the role of maternal factors, like maternal behavior and glucocorticoids, in the prenatal stress-induced changes in adult male rat social behavior, paraventricular nucleus OT expression and OT receptor binding in amygdala, lateral septum and bed nucleus of the stria terminalis. Specific Aim 2. Examine the developmental timing of prenatal stress-induced changes in the brain OT system and social behavior. Specific Aim 3. Examine whether prenatal stress alters the expression of genes that regulate OT components in the developing and adult rat brain. Specific Aim 4. OT reverses the social deficit in prenatally stressed rats when injected into the amygdala. Examine the role of OT receptors in other brain regions to normalize prenatal stress-induced alterations in social behavior. Specific Aim 5. Examine the state of the oxytocinergic system in human schizophrenic hypothalamic and amygdalar tissues. Together these studies will provide new information about a potential etiological agent for schizophrenia; a mechanism by which a schizophrenia-related behavioral abnormality arises and a putative treatment to restore normal social function to affected animals, and potentially human schizophrenics, also.

描述（由申请人提供）：催产素（OT）和加压素的产生集中在下丘脑室旁核和视上核。这些细胞发出的纤维支配参与控制社会行为的边缘脑区域。一些人类疾病，如精神分裂症和自闭症，具有显着的社会表现，对患有这些疾病的个人产生不利影响。大约三分之一的精神分裂症患者患有精神分裂症的阴性症状（例如社交障碍、快感缺失、失语），而目前可用的抗精神病药物无法治疗这些症状。这些症状的生物学基础尚不清楚。我的实验室开发了一种新型动物模型，该模型表现出精神分裂症表型的许多方面，包括社会动力和功能受损。在本申请中，我们建议使用这种动物制剂来研究这些动物表现出的社交无能的病因病理生理学及其与精神分裂症的关系。我们的初步数据表明，大脑OT系统的改变是产前应激雄性大鼠社交功能障碍的诱发因素。因此，我们的总体假设是，产前应激暴露会损害大脑 OT 神经元的发育，催产素能神经元的功能障碍会导致产前应激大鼠以及可能出现阴性症状的精神分裂症患者出现社交功能障碍。为了检验这一假设，提出了以下具体目标。具体目的 1. 探讨母体因素（如母体行为和糖皮质激素）在产前应激引起的成年雄性大鼠社会行为、室旁核 OT 表达以及杏仁核、侧隔和纹状体床核中 OT 受体结合变化中的作用终端。具体目标 2. 检查产前应激引起的大脑 OT 系统和社会行为变化的发育时间。具体目标 3. 检查产前应激是否会改变发育中和成年大鼠大脑中调节 OT 成分的基因表达。具体目标 4. OT 注射到杏仁核后可逆转产前应激大鼠的社交缺陷。检查 OT 受体在其他大脑区域的作用，以使产前压力引起的社会行为改变正常化。具体目标 5. 检查人类精神分裂症下丘脑和杏仁核组织中催产素系统的状态。这些研究将共同​​提供有关精神分裂症潜在病因的新信息；一种与精神分裂症相关的行为异常发生的机制，以及一种为受影响的动物以及潜在的人类精神分裂症患者恢复正常社会功能的假定治疗方法。

项目成果

Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism.

• DOI: 10.1016/j.neuroscience.2010.09.059
• 发表时间: 2010-12-29
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Silverman, J. L.;Yang, M.;Turner, S. M.;Katz, A. M.;Bell, D. B.;Koenig, J. I.;Crawley, J. N.
• 通讯作者: Crawley, J. N.