Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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The 5-HT3 receptor antagonists zacopride and GR38032F are highly effective inhibitors of emesis induced by ionizing radiation and chemotherapeutic drugs such as cisplatin. The present study evaluated zacopride and GR38032F for efficacy in inhibiting the formation of the conditioned taste aversion CTA induced by cisplatin or lithium chloride in rats. The glucocorticoid dexamethasone, which has been reported to be effective against both the emetic and CTA-inducing effects of cisplatin, was included as a reference compound. When administered alone by i.p. injection, zacopride 0.1-10 mgkg, GR38032F 10 mgkg and cisplatin 0.32-1.8 mgkg induced a CTA to an 0.1 saccharin solution lower doses of each compound were ineffective. When administered as a pretreatment, neither zacopride 0.001-0.1 mgkg nor GR38032FO.01-10 mgkg attenuated the CTA induced by cisplatin 0.32 and 0.56 mgkg or lithium chloride 10 mgkg. In contrast, dexamethasone 0.32 and 1.0 mgkg attenuated the CTA induced by 0.32 but not 0.56 mgkg of cisplatin. In an attempt to evaluate higher doses of zacopridc against cisplatin without the potentially confounding factor that these doses by themselves induce a CTA, rats were injected with zacopride on three separate days prior to the aversion conditioning session. This preexposure treatment blocked the formation of the zacopride-induced CTA, but did not improve the efficacy of zacopride in attenuating the cisplatin-induced CTA. These results suggest that neither the cisplatin- nor the lithium-induced CTA in rats are due to effects that are sensitive to 5-HT3 receptor blockade. 5-HT3 receptor antagonists, Zacopride, GR38032F, Dexamethasone, Cisplatin, Taste aversion conditioned.
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