Dexamethasone has a central antiemetic mechanism in decerebrated cats.
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 microg, n = 7; 0.1 microg, n = 7) into the bilateral nuclei tractus solitarii, which led to a significant prolongation of the latency (1 microg, 6.4 +/- 1.1 min versus 28.2 +/- 4.9 min, P < 0.05; 0.1 microg, 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 microg, 2.7 +/- 0.8 versus 0.1 +/- 0.4, P < 0.05; 0.1 microg, 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.
Ho
Chiu-Ming
CM
*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.
Ho
Shung-Tai
ST
Wang
Jhi-Joung
JJ
Tsai
Shen-Kou
SK
Chai
Chok-Yung
CY
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D002415:Cats; D003655:Decerebrate State; D003907:Dexamethasone / Q000494:pharmacology*; D008845:Microinjections; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology
D000932:Antiemetics; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone