MECHANISM OF DEPRESSIVE BEHAVIOR IN WISTAR-KYOTO RATS

WISTAR-KYOTO 大鼠抑郁行为的机制

• 批准号: 6315766
• 负责人: SHANAZ MOHAMMEDALI TEJANI-BUTT
• 金额: $ 12.84万
• 依托单位: UNIVERSITY OF THE SCIENCES PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6315766
• 关键词: adrenocorticotropic hormone; antidepressants; autoradiography; behavioral /social science research tag; biological models; corticosterone; depression; high performance liquid chromatography; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory rat; limbic system; mental disorder chemotherapy; model design /development; molecular pathology; neuroendocrine system; neuropharmacology; neuropsychological tests; neuropsychology; neurotransmitter receptor; nonhuman therapy evaluation; peptic ulcer; psychological stressor; psychosomatic disorders; radioimmunoassay; receptor expression

DESCRIPTION (provided by applicant): The Wistar-Kyoto (WKY) rat has been proposed as a useful animal model in which to study the connection between stress responsiveness and vulnerability to depressive behavior. Physiologically, the WKY rat shows greater susceptibility to stress-induced gastric ulcers than other strains. Endocrine studies report that WKY rats have high levels of stress-induced adrenocorticotropin and low levels of corticotropin releasing hormone, suggesting a defective feedback in the hypothalamic-pituitary-adrenal (HPA) axis. Our research has revealed significant differences in central norepinephrine (NE) and serotonin (5-HT) sites in WKY rats when compared to Sprague-Dawley rats. Treatment with desipramine (a NE uptake blocker), but not paroxetine (a 5-HT uptake blocker), decreased immobility time in the Porsolt forced swim test, and reduced ulcer incidence, implicating the NE system in the mediation of depressive behavior in WKY rats. This grant is aimed at further substantiating the value of the WKY model, and is designed to determine the mechanisms that mediate the disease condition. Differential sensitivity to antidepressants with distinct pharmacological actions may provide useful information regarding the underlying substrates that contribute to a selective response in the WKY rat. Thus the central objective is to ascertain whether antidepressants that target specific neurotransmitter sites in the brain, will alleviate depressive behavior and attenuate the animal's responsiveness to stress. This behavioral response is expected to decrease ulcer susceptibility, modify feedback in the HPA axis, and reverse the characteristic NE and 5-HT receptor alterations in the WKY rat. A positive answer to this objective will provide significant information regarding the mechanisms that underlie depressive behavior and ulcer susceptibility in this vulnerable rat strain. The information gained from this study could provide a better understanding of why a clinical response is observed in some populations of depressed patients, while a resistance in treatment response is seen in others.

描述（由申请人提供）： Wistar-Kyoto (WKY) 大鼠已被 被提议作为一种有用的动物模型来研究之间的联系 压力反应和对抑郁行为的脆弱性。 从生理学角度来看，WKY 大鼠对应激诱导的应激表现出更高的敏感性 胃溃疡的发生率高于其他菌株。内分泌研究报告称 WKY 大鼠 应激引起的高水平促肾上腺皮质激素和低水平的促肾上腺皮质激素 促肾上腺皮质激素释放激素，表明反馈有缺陷 下丘脑-垂体-肾上腺（HPA）轴。我们的研究表明 中枢去甲肾上腺素（NE）和血清素（5-HT）的显着差异 与 Sprague-Dawley 大鼠相比，WKY 大鼠中的位点。治疗用 地昔帕明（一种 NE 摄取阻滞剂），但不是帕罗西汀（一种 5-HT 摄取阻滞剂）， 减少 Porsolt 强迫游泳测试中的不动时间，并减少溃疡 发病率，暗示 NE 系统在抑郁行为的调节中 WKY 大鼠。 这笔赠款旨在进一步证实 WKY 模型的价值，并且 旨在确定介导疾病状况的机制。 对具有不同药理作用的抗抑郁药的敏感性不同 行动可能会提供有关底层基材的有用信息 有助于 WKY 大鼠的选择性反应。因此中心目标 是为了确定抗抑郁药是否针对特定的神经递质 大脑中的位点，将减轻抑郁行为并减弱 动物对压力的反应。这种行为反应预计 降低溃疡易感性，修改 HPA 轴的反馈，并逆转 WKY 大鼠中特征性 NE 和 5-HT 受体改变。积极的 对这一目标的回答将提供有关 抑郁行为和溃疡易感性背后的机制 脆弱的大鼠品系。从这项研究中获得的信息可以提供 更好地理解为什么在某些人群中观察到临床反应 抑郁症患者的治疗反应出现阻力 其他的。

项目成果

Fear conditioning fragments REM sleep in stress-sensitive Wistar-Kyoto, but not Wistar, rats.

• DOI: 10.1016/j.pnpbp.2010.08.023
• 发表时间: 2011-01-15
• 期刊: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
• 影响因子: 5.6
• 作者: DaSilva, Jamie K.;Lei, Yanlin;Madan, Vibha;Mann, Graziella L.;Ross, Richard J.;Tejani-Butt, Shanaz;Morrison, Adrian R.
• 通讯作者: Morrison, Adrian R.

Strain differences in the distribution of dopamine (DA-2 and DA-3) receptor sites in rat brain.

大鼠脑中多巴胺（DA-2 和 DA-3）受体位点分布的应变差异。

• DOI: 10.1016/j.lfs.2006.02.030
• 发表时间: 2006
• 期刊: Life sciences.
• 作者: Yaroslavsky,Irene;Colletti,Michael;Jiao,Xilu;Tejani-Butt,Shanaz
• 通讯作者: Tejani-Butt,Shanaz