Preclinical assessment core

临床前评估核心

• 批准号: 7483509
• 负责人: JAMES I KOENIG
• 金额: $ 14.2万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483509
• 关键词: Adult; Animal Model; Animals; Antimitotic Agents; Behavior; Behavioral; Behavioral Symptoms; Bereavement; Brain; Characteristics; Clinical; Clinical Trials; Cognition; Complex; Data; Development; Disease; Drug usage; Effectiveness; End Point; Exhibits; Female; Generations; Genes; Genetic Models; Hippocampus (Brain); Human; Immune; Impaired cognition; Impairment; Incidence; Investigation; Knock-out; Lesion; Literature; Malnutrition; Modeling; Mus; Natural Disasters; Nature; Neonatal; Nicotinic Receptors; Outcome Measure; Oxytocin; Oxytocin Receptor; Patient currently pregnant; Patients; Pharmaceutical Preparations; Phencyclidine; Phenotype; Pre-Clinical Model; Pregnancy; Pregnant Women; Preparation; Purpose; Rattus; Reporting; Risk; Schizophrenia; Second Pregnancy Trimester; Series; Staging; Stress; Symptoms; System; Testing; Time; Virus Diseases; Week; Withdrawal; Work; anabaseine; base; cognitive function; drug development; functional outcomes; male; novel; pre-clinical; preclinical study; prenatal; prenatal stress; prepulse inhibition; receptor expression; social

and the cognitive impairments are robustly associated with poor functional outcomes. This CIDAR application embraces the notion that novel preclinical and clinical approaches are necessary for the development of new therapies for the negative symptom and cognitive impairment domains of schizophrenia. We have generated a novel pre-clinical animal preparation based on developmental and epidemiological data showing that mid-gestational stress exposure increases the risk for developing schizophrenia and is termed the unpredictable prenatal stress model of schizophrenia (PSup). The PSup model is ideally suited to launch a translational investigation of novel drugs for use in treating schizophrenia because the behavioral phenotype of the rats displays similarity to the behavioral symptoms of schizophrenic patients and thte enduring nature of the behavioral changes. Using the PSup animal preparation, we have generated exciting pre-clinical findings showing beneficial effects of oxytocin on social withdrawal behavior exhibited by the PSup rats. These data support the hypothesis that oxytocin may produce beneficial effects in clinical and pre-clinical models of the negative symptoms of schizophrenia, as proposed in this CIDAR application and in Projects #1, 2 and 3. Additionally, PSup rats will be used to evaluate whether significant cliniclal findings regarding the alpha? nicotinic receptor and cognition can be extended to the pre-clinical situation. The overall hypothetical framework for this CIDAR application is based on the following propositions: 1) that negative symptoms and cognitive impairments may be separate clinical targets for drug development, and a drug with efficacy for one domain may not have an effect on the other; 2) that a drug effect on a domain in a clinical trial will be associated with a similar effect in a pre-clinical rat model and a non-clinical human model and 3) that oxytocin receptor stimulation and alpha-7 nicotinic receptor stimulation will benefit behaviors relating to the negative symptoms and cognitive impairments of schizophrenia, respectively. The purpose of the Pre-clinical Studies Core is to generate the PSup rats needed to pursue the studies proposed in Project #1 of this CIDAR application and to establish the platform of behavioral outcome measures needed to evaluate the predictive validity of testing the selected compounds in the PSup animal preparation.

并且认知障碍与功能不良的结果牢固相关。这个Cidar 应用包含这样的观念，即新颖的临床前和临床方法是必要的 开发精神分裂症的负面症状和认知障碍领域的新疗法。 我们已经基于发育和流行病学产生了一种新型的临床前动物制备 数据表明，妊娠压力暴露会增加发展精神分裂症的风险，IS 被称为精神分裂症（PSUP）的不可预测的产前应力模型。 PSUP模型非常适合 由于行为性，推出用于治疗精神分裂症的新型药物的翻译调查 大鼠的表型显示与精神分裂症患者的行为症状相似 行为变化的持久性质。使用PSUP动物准备，我们产生了令人兴奋的 临床前发现显示催产素对社会戒断行为的有益影响 PSUP大鼠。这些数据支持催产素可能在临床和 该cidar应用和在 项目＃1、2和3。此外，PSUP大鼠将用于评估是否重要的​​临床发现 关于alpha？烟碱受体和认知可以扩展到临床前的情况。 该CIDAR应用程序的总体假设框架基于以下命题：1） 负面症状和认知障碍可能是药物开发的单独临床目标，并且 对一个领域有效的药物可能不会对另一个领域产生影响； 2）对域中的药物影响 临床试验将与临床前大鼠模型和非临床人类模型的类似作用有关 3）催产素受体刺激和α-7烟碱受体刺激将使行为受益 分别与精神分裂症的负面症状和认知障碍有关。目的 临床前研究的核心是产生追求项目中提出的研究所需的PSUP大鼠 本封装应用的＃1，并建立所需的行为结果措施的平台 评估测试PSUP动物制剂中所选化合物的预测有效性。