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mCPP 诱导的大鼠刻板咀嚼行为是强迫症的动物模型。

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

机构信息

University of Tennessee at Chattanooga, Department of Biological and Environmental Sciences, 615 McCallie Avenue, Chattanooga, TN 37403, USA.

出版信息

Pharmacol Biochem Behav. 2013 Mar;104:119-24. doi: 10.1016/j.pbb.2013.01.006. Epub 2013 Jan 17.

Abstract

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD.

摘要

强迫症(OCD)的特征是反复出现的、引起焦虑的想法,伴随着执行仪式性行为的无法控制的强烈冲动。针对这种疾病的药物治疗(血清素摄取抑制剂)存在问题,因为它有 6-8 周的延迟发作,而且一半的患者反应不充分。本研究评估了血清素激动剂 mCPP 在大鼠中引起的刻板咀嚼行为(RCBs)是否是 OCD 的行为模型。在用血清素拮抗剂米氮平(3mg/kg)、多巴胺拮抗剂氟哌啶醇(1mg/kg)、GABA 调节剂地西泮(10mg/kg)或血清素摄取抑制剂氯米帕明和氟伏沙明(15mg/kg)治疗后,评估了 mCPP 诱导的 RCBs 的影响。米氮平的急性治疗阻断了 mCPP 的反应,但急性氟哌啶醇或地西泮的治疗没有阻断。进一步的实验表明,米氮平和氟伏沙明的慢性治疗而非急性治疗阻断了 mCPP 的作用。时间进程表明,需要 14 天的慢性治疗才能阻断 mCPP 诱发的反应。本研究表明,mCPP 诱发的 RCBs 可能是 OCD 的啮齿动物模型,可用于预测新型 OCD 治疗的临床疗效和时间进程。未来的研究可能能够使用当前模型作为基准工具,用于衡量其他神经活动测量指标的相应变化,这可能有助于深入了解 OCD 的机制。

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