Neuropeptide Involvement In Male Social Behavior

神经肽参与男性社会行为

• 批准号: 7032684
• 负责人: JAMES I KOENIG
• 金额: $ 26.38万
• 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032684
• 关键词: adrenalectomy; amygdala; animal developmental psychology; animal puberty; autoradiography; behavior test; behavioral /social science research tag; brain septal area; catheterization; corticosterone; developmental neurobiology; disease /disorder etiology; gene expression; hormone receptor; hormone regulation /control mechanism; human tissue; laboratory rat; male; maternal behavior; neuropsychology; oxytocin; paraventricular nucleus; postmortem; prenatal stress; radioimmunoassay; receptor binding; schizophrenia; social behavior disorders; transcription factor; vasopressins

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旁脑室和上型核中。从这些细胞中产生的纤维影响了与社会行为控制有关的边缘大脑区域。一些人类疾病，例如精神分裂症和自闭症，具有突出的社会表现形式，对患有这些疾病的个体产生了不利影响。大约有三分之一的精神分裂症患者患有精神分裂症的负面症状（例如，社会性，Anhedonia，言语的吸收），这些症状未被当前可用的抗精神病药物治疗。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的动物模型，该模型表现出精神分裂症表型的许多方面，包括受损的社交驱动器和功能。在此应用中，我们建议利用这种动物的准备来研究这些动物表现出的社会无能的病理学及其与精神分裂症的关系。我们的初步数据指出，大脑OT系统的改变是产前压力男性大鼠社会功能障碍的降水因素。因此，我们的总体假设是，产前压力暴露损害了脑OT神经元的发展，催产蛋白能神经元的功能障碍会在产前压力大鼠中产生社会功能障碍，并可能在患有阴性症状的精神分裂症患者中。为了检验该假设，提出了以下特定目标。具体目的1。检查产妇因素（如母体行为和糖皮质激素）在成年男性大鼠社交行为，乳腺胞核表达和OT受体结合的成年雄性大鼠社交行为的变化中的作用。特定目的2。检查产前压力引起的大脑OT系统和社会行为变化的发育时机。特定目的3。检查产前应力是否改变了调节发育中和成年大鼠大脑中OT成分的基因的表达。特定目的4。当注射到杏仁核中时，OT会逆转产前压力大鼠的社会缺陷。检查OT受体在其他大脑区域中的作用，以使产前压力诱导的社会行为改变。具体目的5。检查人类精神分裂症下丘脑和杏仁核组织中催产毒素能系统的状态。这些研究将共同​​提供有关精神分裂症潜在病因学剂的新信息。精神分裂症相关的行为异常和假定的治疗方法是恢复受影响动物以及潜在的人类精神分裂症患者的正常社会功能的一种机制。