HORMONES IN CAUSE AND TREATMENT OF AFFECTIVE DISORDERS

激素导致情感障碍和治疗

• 批准号: 3076050
• 负责人: ARTHUR J. PRANGE
• 金额: $ 5.96万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3076050
• 关键词: antidepressants; hormone regulation /control mechanism; human subject; imipramine; insulin; mental disorder chemotherapy; neurohormones; neurotensin; oxytocin; phenobarbital; psychopharmacology; schizophrenia; thyrotropin; thyrotropin releasing hormone; tranquilizer; triiodothyronine

In the laboratory, work will be addressed to three endogenous neuropeptides, oxytocin (OXY), neurotensin (NT) and thyrotropin-releasing hormone (TRH). Work with OXY will focus on the property of this peptide to produce maternal behavior in virgin female rats. Interest is now focused on blocking the action of endogenous OXY in triggering this behavior in a variety of circumstances. Neurotensin is of interest because many of its actions run parallel to those of neuroleptic drugs. We propose to identify the sites in brain where NT enhances pentobarbital-induced sleeping time and where it enhances pentobarbital-induced hypothermia. Additional studies bear upon the role of NT in thermoregulation. While NT prolongs pentobarbital-induced sleeping time, TRH shortens it. We will use this property of TRH to study the action of putative inhibitors of TRH synthesis and inhibitors of TRH degradation. Additional studies are addressed to probable interactions between TRH and NT. In the clinic, work will focus on three endogenous peptides: NT, TRH, and insulin. Because NT can blunt the TSH response to TRH it will be of interest to discern whether patients with blunted responses have altered levels of NT in spinal fluid. The TSH response to TRH will also be studied as regards its characteristics in a large population of normals and its possible influence by stage of the menstrual cycle. Its possible value in predicting the efficacy of L-triiodothyronine as an adjunct to imipramine in depression will also be studied. The behavioral and endocrine effects of insulin will be studied in normal subjects and schizophrenic patients while hypoglycemia is prevented by glucose administration. These studies are prompted in part by recent observations that not all endocrine effects of insulin are due to hypoglycemia. This broad program of research into the behavioral and predictive properties of peptide hormones in both animals and man will involve a variety of techniques and a number of collaborators skilled in their special application.

在实验室中，工作将针对三个内源性 神经肽，催产素（OXY），神经降压素（NT）和促甲状腺激素释放激素 激素（TRH）。 与OXY的合作将集中在这种肽的特性上， 在未交配的雌性大鼠中产生母性行为。 现在的兴趣集中在 阻断内源性氧合酶的作用， 各种各样的情况。 神经降压素之所以令人感兴趣，是因为它的许多 作用与精神抑制药的作用类似。 我们建议确定 脑内NT增强戊巴比妥诱导睡眠时间的部位 并增强戊巴比妥引起的体温过低 额外 研究表明NT在体温调节中的作用。 虽然NT 戊巴比妥诱导的睡眠时间，TRH缩短它。我们将使用这个 TRH的性质，以研究TRH合成的假定抑制剂的作用 和TRH降解的抑制剂。 其他研究涉及 TRH和NT之间的相互作用。 在临床上，工作将集中在三种内源性肽：NT、TRH和 胰岛素 因为NT可以减弱TSH对TRH的反应， 感兴趣的是辨别反应迟钝的患者是否改变了 脊髓液中NT水平。 TSH对TRH的反应也将被研究 关于其在大量正常人群中的特征及其 可能受月经周期阶段的影响。 其可能的价值在于 预测L-三碘甲状腺原氨酸作为丙咪嗪辅助治疗的疗效 抑郁症也将被研究。 行为和内分泌影响 将在正常受试者和精神分裂症患者中研究胰岛素 而低血糖症通过葡萄糖给药来预防。 这些研究 部分是由于最近的观察，不是所有的内分泌影响， 低血糖是由于低血糖。 这个广泛的研究项目是关于行为和预测 肽激素在动物和人类中的特性将涉及 各种各样的技术和一些合作者在他们的熟练 特殊应用。