Altered feeding behaviour induced by long-term cisplatin in rats
Altered feeding behaviour induced by long-term cisplatin in rats
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DOI：
10.1016/j.autneu.2006.02.011
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发表时间：
2006-06-30
影响因子：
2.7
通讯作者：
Abalo, Raquel
中科院分区：
文献类型：
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作者：
Vera, Gema;Chiarlone, Anna;Abalo, Raquel
在没有呕吐反射的动物中，几种致吐性刺激会引起异食癖，这是一种由摄入非营养性物质组成的摄食行为改变。异食癖的发展是对致吐刺激的反应，被认为是大鼠恶心的间接标志。事实上，就像人类的恶心和呕吐一样，它伴随着肠染色质细胞的血清素释放，后脑区和孤束核的c-fos标记增加，胃排空延迟。此外，异食癖（以高岭土摄入量来衡量）可以通过止吐药物来减少。单剂量顺铂（最具致吐性的化疗药物）已被证实可引起异食癖。然而，顺铂和其他抗肿瘤药物一样，通常是周期性给药，而传统的止吐药往往会失去效果。本研究的目的是评价顺铂长期治疗引起的异食癖。每周给予生理盐水或顺铂1次，连续5周，每天测量体温、体重、摄食量和高岭土摄入量。隔离（异食癖必须在孤立动物中进行研究）和暴露于高岭土（基础高岭土摄入量可以改变异食癖本身和其他参数）对盐处理大鼠的体温、体重和每日食物摄取量的影响可以忽略不计。给药剂量为3mg /kg/周的顺铂毒性太大：在分组和离体大鼠中均产生低温、体重下降和厌食，离体动物死亡率为50%。每周一毫克/公斤顺铂的毒性是可以接受的，主要效果是体重增加速度较慢。在这些大鼠中，每次顺铂注射均产生急性厌食和反跳性贪食反应。此外，每次给药都会引起急性异食癖和基础高岭土摄入量的增加，类似于人类恶心的发展。该模型可用于研究与长期抗肿瘤治疗相关的恶心机制和新型止吐药物的有效性。(c) 2006 Elsevier B.V.保留所有权利。
In animals without the emetic reflex, several emetogenic stimuli induce pica, an altered feeding behaviour consisting of the ingestion of non-nutritive substances. The development of pica in response to an emetogenic stimulus has been proposed to be useful as an indirect marker of nausea in the rat. In fact, like nausea and emesis in humans, it is accompanied by serotonin release from the enterochromaffin cells, increased c-fos labelling in the area postrema and the nucleus tractus solitarius, and a delay in gastric emptying. Furthermore, pica, measured as kaolin intake, is reduced by anti-emetic drugs. Pica has been demonstrated after single doses of cisplatin, the most emetogenic chemotherapeutic drug. However, cisplatin, as other antineoplastic drugs, is generally given in cycles, where conventional anti-emetics tend to lose efficiency. The aim of this work was to evaluate the pica induced by long-term treatment with cisplatin. Saline or cisplatin was administered once a week for 5 consecutive weeks, and temperature, body weight, food ingestion and kaolin intake were measured on a daily basis. The influence of isolation (pica is necessarily studied in isolated animals) and exposure to kaolin (basal kaolin intake could modify pica itself and other parameters) on temperature, body weight and daily food ingestion was negligible in saline-treated rats. Cisplatin administered at 3 mg/kg/week was too toxic: it produced hypothermia, weight drop and anorexia in both grouped and isolated rats, and 50% mortality in isolated animals. Toxicity associated with cisplatin administered at I mg/kg/week was acceptable, with a slower rate of weight gain being the major effect. In these rats, each cisplatin injection produced both acute anorexia and rebound hyperphagic responses. In addition, each administration induced both acute pica and an increase in basal kaolin intake, resembling the development of nausea in humans. This model could be useful for studying both the mechanisms leading to nausea associated with a long-term antineoplastic treatment and the efficiency of new anti-emetic drugs. (c) 2006 Elsevier B.V. All tights reserved.