Validation of the xylazine/ketamine anesthesia test as a predictor of the emetic potential of pharmacological compounds in rats
| Autor: | Caroline Wouters, Britt T. J. van Hagen, Pim R. A. Heckman, Vivian T. Bonassoli, Ellis Nelissen, Jos Prickaerts, Dila Suay, Nick P. van Goethem |
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| Přispěvatelé: | Havekes lab, Promovendi MHN, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Xylazine Time Factors Drug-Related Side Effects and Adverse Reactions Vomiting medicine.drug_class Drug Evaluation Preclinical PDE4 INHIBITORS Imipramine MECHANISMS 03 medical and health sciences 0302 clinical medicine CLONIDINE medicine Animals Anesthesia Ketamine Phosphodiesterase Rolipram RELEASE RECEPTOR business.industry General Neuroscience AREA POSTREMA Nausea Receptor antagonist Emesis LOCUS-CERULEUS Rats Clonidine Yohimbine 030104 developmental biology alpha 2 adrenergic receptor Alpha-2 adrenergic receptor CERULEUS NORADRENERGIC NEURONS business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience Letters, 699, 41-46. ELSEVIER IRELAND LTD Neuroscience Letters, 699, 41-46. Elsevier Ireland Ltd |
| ISSN: | 0304-3940 |
| Popis: | The xylazine/ketamine anesthesia test is widely used as a predictor of the emetic potential of pharmacological compounds in rats. An emetic reflex is usually triggered by the emetic center, which is populated with many different chemoreceptors. Inhibition of the alpha 2 adrenergic receptor (alpha 2 receptor) is involved in the initiation of the emetic reflex, and this is the key mechanism behind the xylazine/ketamine anesthesia test. In this study, we attempt to validate this test as a predictor of the emetic potential of pharmacological compounds. Furthermore, it was investigated whether an anti-emetic potential of pharmacological compounds could be assessed within this test as well. Rats were anesthetized with a combination of low doses of ketamine and xylazine, and subsequently treated with PDE4 inhibitor rolipram, alpha 2 receptor antagonist yohimbine, alpha 2 receptor agonist clonidine, tricyclic antidepressant imipramine, D2-receptor antagonist haloperidol, or 5-HT3 receptor antagonist (and anti-emetic drug) ondansetron. We were able to successfully reproduce the reduction in anesthesia time after rolipram or yohimbine treatment, as found in previous studies and has been suggested to be indicative of emetic properties of these treatments is humans. Furthermore, clonidine shortened anesthesia duration whereas imipramine and haloperidol lengthened anesthesia duration. Ondansetron was unable to rescue the reduction in duration of anesthesia induced by either rolipram or yohimbine. Altogether, the xylazine/ketamine anesthesia test is a reliable measure for alpha 2 receptor antagonism. However, it may not be appropriate to assess emesis independent of this mechanism. |
| Databáze: | OpenAIRE |
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