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ANESTHETIC PHARMACOLOGY

Dexamethasone Has a Central Antiemetic Mechanism in Decerebrated Cats

Chiu-Ming Ho, MD PhD^*, Shung-Tai Ho, MD MS, Jhi-Joung Wang, MD DMSc, Shen-Kou Tsai, MD PhD^*, and Chok-Yung Chai, MD PhD

*Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan; Department of Anesthesiology, National Defense Medical Center/Tri-Service General Hospital, Taipei, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Address correspondence and reprint requests to Shung-Tai Ho, MD, MS, Department of Anesthesiology, National Defense Medical Center/Tri-Service General Hospital, Rm. 8113, No. 161, Sec. 6, Minchiuan E. Rd., Taipei 114, Taiwan. Address e-mail to painlab{at}tpts5.seed.net.tw

Dexamethasone is an effective antiemetic drug, but its mechanism of action is unclear. We designed this study to investigate the direct antiemetic action of dexamethasone in the medulla of cats. By using an oscillographic vomiting model, decerebrated cats received microinjections of dexamethasone 100 nL (1 µg, n = 7; 0.1 µg, n = 7) into the bilateral nuclei tractus solitarii, which led to a significant prolongation of the latency (1 µg, 6.4 ± 1.1 min versus 28.2 ± 4.9 min, P < 0.05; 0.1 µg, 6.7 ± 1.1 min versus 27.1 ± 5.0 min, P < 0.05) of the first emetic episode and significantly decreased the frequency of emetic episodes (1 µg, 2.7 ± 0.8 versus 0.1 ± 0.4, P < 0.05; 0.1 µg, 2.9 ± 0.9 versus 0.3 ± 0.5, P < 0.05) induced by xylazine. Pretreatment with mifepristone, a glucocorticoid receptor antagonist, blocked the antiemetic effect of dexamethasone in the bilateral nuclei tractus solitarii. However, microinjection of dexamethasone into the unilateral nucleus tractus solitarius alone did not alter the latency of the first emetic episode or the frequency of emetic episodes induced by xylazine. Local application of dexamethasone into the area postrema had no effect on the latency of the first emetic episode or the frequency of emetic episodes induced by xylazine. These results suggest that dexamethasone exerts its central antiemetic action through an activation of the glucocorticoid receptors in the bilateral nuclei tractus solitarii in the medulla.

IMPLICATIONS: Dexamethasone has an antiemetic property, but the mechanism remains unclear. An oscillographic vomiting model was used in unanesthetized and decerebrated cats to demonstrate that a stereotaxic microinjection of dexamethasone had an antiemetic effect against xylazine-induced emesis by acting on glucocorticoid receptors in the bilateral nuclei tractus solitarii.

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