Cisplatin-induced conditioned taste aversion: attenuation by dexamethasone but not zacopride or GR38032F
| Autor: | John R. McDonough, Kevin P. O'Halloran, David B. McLean, Paul C. Mele |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Lithium Dexamethasone Zacopride Bridged Bicyclo Compounds Taste Disorders chemistry.chemical_compound Chlorides Internal medicine medicine Animals Antiemetic cardiovascular diseases Saccharin Pharmacology Cisplatin Analysis of Variance Dose-Response Relationship Drug Rats Inbred Strains Bridged Bicyclo Compounds Heterocyclic Ondansetron Rats Endocrinology chemistry Benzamides Toxicity Taste aversion Antiemetics Serotonin Antagonists Lithium Chloride psychological phenomena and processes Glucocorticoid medicine.drug |
| Zdroj: | European Journal of Pharmacology. 218:229-236 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(92)90173-2 |
| Popis: | The 5-HT 3 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 mg/kg), GR38032F (10 mg/kg) and cisplatin (0.32–1.8 mg/kg) 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 mg/kg) nor GR38032F (0.01–10 mg/kg) attenuated the CTA induced by cisplatin (0.32 and 0.56 mg/kg) or lithium chloride (10 mg/kg). In contrast, dexamethasone (0.32 and 1.0 mg/kg) attenuated the CTA induced by 0.32 but not 0.56 mg/kg of cisplatin. In an attempt to evaluate higher doses of zacopride 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 pre-exposure 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-HT 3 receptor blockade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|