Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats

Malik, Nasser; Liu, Yong-Ling; Cole, Nicholas; Sanger, Gareth J.; Andrews, Paul

doi:10.1016/j.ejphar.2006.10.043

Cited by 68 publications

(85 citation statements)

References 41 publications

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“…Antiemetic drugs administered for the side effects of cancer chemotherapy are thought to act at the 5-HT receptor on the adjacent vagal afferent nerve in the human, ferret or house musk shrews [2,5,16]. Administration of a 5-HT 3 antagonist has also been reported to attenuate kaolin consumption induced by anticancer drugs [13,22] and X-ray irradiation [31] in rats, but there is no report examining the effects of 5-HT 3 antagonist on the 5-HT or 5HIAA levels in the central nervous system (CNS) in rats showing pica behavior. In the present study, we examined the effects of ondansetron on pica behavior and 5HIAA levels in CSF in rats treated with cyclophosphamide.…”

Section: Discussionmentioning

confidence: 99%

“…Effects of cyclophosphamide on kaolin consumption, food consumption and body weights in the five rat strains: The kaolin was given 3 days before the cyclophosphamide treatment to allow the rats to be acclimated to the presence of kaolin in the cage [12,13,22]. Kaolin and food were provided in a separate compartment in the food containers.…”

Section: Animals and Kaolin Preparationmentioning

confidence: 99%

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Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Tohei

Kojima

Ikeda

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT 3 antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis. Cancer chemotherapy with cyclophosphamide or cisplatin is usually associated with nausea or vomiting in humans [1,2,5,8,16]. These cytotoxic drugs can induce emesis in ferrets [8] and house musk shrews [14,20], and these two animal species have been often used in experiments for emesis. However, studies on the mechanisms of emesis in common laboratory animals such as rats and mice are limited due to the lack of vomiting reflex in rats and mice [8]. Although rats and mice do not vomit, they show pica behavior (the consumption of non-nutritive substances such as kaolin) in response to the various emetic stimuli [7,12,24,[30][31][32]. In rats, pica behavior can be induced by administration of cancer chemotherapy agents [11-13, 18, 22], lithium chloride [18,32], copper sulphate [32] and by motion exposure [7,24]. This behavior is recognized as an index of emesis, and the kaolin ingestion model can be used as a quantifiable behavioral assay of toxins [8,15]. In previous reports, Long Evans (LE) and Wistar rats were mainly used in experiments for pica behavior [11-13, 18, 22], but the reasons why these two strains have been used in this field of study are unclear. There has been no study comparing the expression of pica induced by any emetic stimuli among several strains of rats. In order to choose the best strain of rat for future pica research, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior using Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and LE adult male rats in the present s...

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Section: Discussionmentioning

confidence: 99%

Section: Animals and Kaolin Preparationmentioning

confidence: 99%

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Tohei

Kojima

Ikeda

et al. 2011

The Journal of Veterinary Medical Science

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“…Several other attempts to estimate drug-induced nausea and emesis in rodents have been reported previously (Mitchell et al, 1976;Yamamoto et al, 2005Yamamoto et al, , 2007Malik et al, 2007), but the methods need care. For example, pica behavior, the eating of non-nutritive substances such as kaolin, is known to evaluate emetic potential in rodents (Yamamoto et al, 2007).…”

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confidence: 99%

Solid gastric emptying mediated by the serotonin (5-HT)3 receptor in mice is a simple marker to predict emesis

Ando

Takagi²

2011

J. Toxicol. Sci.

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“…The brains were removed and placed in 10% sucrose/PBS followed by 20% and 30% sucrose/PBS, each for 24 h. After cryoprotection in sucrose, the brains were blocked, frozen on dry ice, and cut coronally in three series at 50 m using a freezing microtome. After perfusion, stomachs were also removed and weighed because reduced gastric emptying is an indicator of the efficacy of the cisplatin treatment (29).…”

Section: Experiments 1: Cisplatin-induced C-fos Expressionmentioning

confidence: 99%

“…Similar to the action of cisplatin on emesis (1, 7, 50), cisplatin-induced kaolin consumption in the rat is largely dependent on an intact subdiaphragmatic vagus (10) and is inhibited by common antiemetic drugs, such as 5-HT 3 and NK 1 receptor antagonists, as well as by corticosteroids (29,49,60). Cisplatin also activates GI vagal afferent fibers in the rat and ferret, a response that is blocked by antagonism of 5-HT 3 receptors (15, 24).…”

mentioning

confidence: 98%

Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

Horn

Jonghe

Mátyás

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Horn CC, De Jonghe BC, Matyas K, Norgren R. Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat. Am J Physiol Regul Integr Comp Physiol 297: R1375-R1382, 2009. First published August 26, 2009 doi:10.1152/ajpregu.00284.2009.-Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatininduced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls (ϳ30 g vs. ϳ5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.emesis; nausea; pica; vagus; anorexia CANCER CHEMOTHERAPY AGENTS, such as cisplatin, stimulate nausea, vomiting, anorexia, and other behaviors indicative of malaise (for a review, see Refs. 2, 21, 27, 51). Several species, including dogs, cats, ferrets, pigs, and shrews, have been used to study emesis after treatment with chemotherapy agents (16,18,31,33,58). In contrast, laboratory rats and mice appear to lack a vomiting response (see Ref. 2 for review). For these species, kaolin intake has been used as a proxy for emesis (60,64). A wide variety of stimuli, including cisplatin, induce kaolin consumption in rats (36,53,59,60,65). Like emesis, geophagia appears to be a defensive response. Clay may serve to bind or dilute a toxin in the gastrointestinal (GI) tract, thus reducing its adverse effects (45, 46). After injection with cisplatin, rats consuming kaolin show less body weight loss and a smaller reduction in food intake than rats without kaolin access (12). The consumption of clay by humans is also recognized as a potential detoxification strategy (48).Despite the use of kaolin intake as an index of malaise in rats, very little is known about...

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Differential effects of dexamethasone, ondansetron and a tachykinin NK1 receptor antagonist (GR205171) on cisplatin-induced changes in behaviour, food intake, pica and gastric function in rats

Cited by 68 publications

References 41 publications

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Effects of Cyclophosphamide on the Kaolin Consumption (Pica Behavior) in Five Strains of Adult Male Rats

Solid gastric emptying mediated by the serotonin (5-HT)3 receptor in mice is a simple marker to predict emesis

Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

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