Author: 〇蘇 韶懿、保浦 七愛、吉澤 知彦、乾 賢、舩橋 誠
Affiliation: 北大 院歯 口腔生理
Abstract:
Purpose: The present study investigated the effects of area postrema lesions and bilateral subdiaphragmatic afferent vagotomy on emetine- and cisplatin-induced taste avoidance in rats, to demonstrate the induction mechanism of nausea and/or emesis by these drugs.
Materials & Methods: Male Sprague-Dawley rats (6-7 weeks old) were used. We evaluated the emetine-induced conditioned taste avoidance (CTA) by measures of saccharin consumption in 3 groups of animals: a bilateral subdiaphragmatic afferent vagotomy group (VX), an area postrema lesion group (APX), and a sham lesion group (Sham), and cisplatin-induced CTA in rats with both area postrema lesions and vagotomy and rats with sham surgery. After acclimatization to water deprivation, rats were conditioned with 1% saccharin solution paired with the administration of cisplatin (3mg/kg, 1%BW, i.p.) or emetine (5.54mg/kg, 1%BW, i.p.). Some rats had pre-administration of dexamethasone (1mg/kg, 0.1%BW, i.p.)30 minutes before the administration of cisplatin. The saccharin intake for 30 minutes on each test day was compared with that on the conditioning day using Dunnett's multiple comparison test. P value less than 0.05 is considered statistically significant. All data are represented as mean ± SEM.
Results & Conclusion: Both emetine and cisplatin produced CTA in all rats in the sham group (n = 5 in each). The emetine-induced CTA was produced in the VX group, but not in the APX group (n = 5 in each). Although cisplatin-induced CTA was still produced in rats with both area postrema lesions and vagotomy (n = 4), pretreatment with the administration of dexamethasone 30 minutes before the conditioning significantly suppressed cisplatin-induced CTA on test days 1 and 2 (n = 6). These results suggest that 1) the input via the area postrema is essential to the induction of emetine-induced CTA, 2) cisplatin-induced CTA may be produced by different neural pathways from that induced by emetine, and 3) dexamethasone may interfere with the production of cisplatin-induced CTA via the action site except the area postrema and vagal afferent inputs.
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