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奥氮平可降低患基于活动的厌食症大鼠的身体活动:对神经性厌食症治疗可能有何启示?

Olanzapine reduces physical activity in rats exposed to activity-based anorexia: possible implications for treatment of anorexia nervosa?

作者信息

Hillebrand Jacquelien J G, van Elburg Annemarie A, Kas Martien J H, van Engeland Herman, Adan Roger A H

机构信息

Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.

出版信息

Biol Psychiatry. 2005 Oct 15;58(8):651-7. doi: 10.1016/j.biopsych.2005.04.008. Epub 2005 Jul 14.

Abstract

BACKGROUND

Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduces the development of ABA in rats. The effect of olanzapine treatment in AN patients was also evaluated in a small open-label study.

METHODS

Rats were chronically (1 week) infused with olanzapine (7.5 mg/kg) and exposed to the ABA model or ad libitum feeding. Hyperactive AN patients were followed for up to 3 months of olanzapine treatment (5 mg/kg).

RESULTS

Olanzapine treatment reduced development of ABA in rats by reducing running wheel activity, starvation-induced hypothermia and activation of the hypothalamus-pituitary-adrenal axis. Olanzapine treatment reduced activity levels of AN patients compared with untreated AN patients, without affecting body weight and plasma leptin levels.

CONCLUSIONS

Olanzapine treatment reduced wheel running and thereby diminished development of ABA in rats. Olanzapine treatment also reduced physical activity in hyperactive AN patients in a small open-label study. These data support the need for controlled studies investigating the putative beneficial effects of olanzapine treatment in AN patients.

摘要

背景

神经性厌食症(AN)患者常表现出极度食欲减退和过度体力活动。基于活动的厌食症(ABA)被认为是AN的动物模型,可模拟大鼠的食物限制和多动情况。本研究调查了奥氮平(再普乐)治疗是否能减少大鼠ABA的发展。还在一项小型开放标签研究中评估了奥氮平治疗对AN患者的影响。

方法

大鼠长期(1周)输注奥氮平(7.5毫克/千克),并暴露于ABA模型或自由进食状态。对多动的AN患者进行长达3个月的奥氮平治疗(5毫克/千克)随访。

结果

奥氮平治疗通过降低转轮活动、饥饿诱导的体温过低以及下丘脑 - 垂体 - 肾上腺轴的激活,减少了大鼠ABA的发展。与未治疗的AN患者相比,奥氮平治疗降低了AN患者的活动水平,且不影响体重和血浆瘦素水平。

结论

奥氮平治疗减少了大鼠的转轮活动,从而减少了ABA的发展。在一项小型开放标签研究中,奥氮平治疗也降低了多动的AN患者的体力活动。这些数据支持需要进行对照研究,以调查奥氮平治疗对AN患者的假定有益作用。

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