Effect of Different Doses of Atipamezole on Reversal of Medetomidine-Induced Tear-Flow Decrease in Rats.

Teppei Kanda,Yuki Shimizu,Kayo Furumoto,Manami Gotoh,Noritaka Maeta,Ayumi Makino,Toshinori Furukawa,Takamasa Itoi

doi:10.3390/vetsci7040197

Abstract

It has been reported that α2-adrenoceptor agonists such as medetomidine decrease tear flow in many species, including rats. Few studies have investigated the involvement of α2-adrenoceptor in decreased tear flow; the issue has not been illustrated sufficiently. Therefore, we aimed to investigate the effect of different doses of atipamezole on the reversal of medetomidine-induced tear-flow decrease to reveal the specific involvement of α2-adrenoceptor. Treatment with 400, 800, or 1600 µg/kg atipamezole (or saline as the control) was intramuscularly administered to rats 15 min following intramuscular administration of 200 µg/kg medetomidine. After medetomidine administration, tear flow was measured using a phenol red thread test (PRTT). PRTT values decreased significantly after 200 µg/kg medetomidine administration. The PRTT values after 800 (optimal dose to reverse) and 1600 µg/kg atipamezole administration reached baseline, but never exceeded it significantly. Treatment with 400 µg/kg atipamezole also reversed the decrease in PRTT value but the PRTT remained lower than baseline. The optimal dose and the higher dose of atipamezole fully reversed the medetomidine-induced decrease in tear flow to the baseline level in rats, while the lower dose of atipamezole partially recovered tear flow.

Highlights

Medetomidine, a representative α2 -adrenoceptor agonist, is widely used for sedation or analgesia of many species in veterinary medicine [1,2,3,4]
From 5 to 55 min after administration, 800 and 1600 μg/kg atipamezole significantly reversed the decrease in phenol red thread test (PRTT) compared to the value 15 min after medetomidine administration in each group
While 400 μg/kg atipamezole showed a tendency to reverse the decrease in PRTT value at 5 min after administration; the PRTT value was significantly lower than the baseline value at that time

Summary

Introduction

Medetomidine, a representative α2 -adrenoceptor agonist, is widely used for sedation or analgesia of many species in veterinary medicine [1,2,3,4]. Do α2 -adrenoceptor agonists, including medetomidine, act as sedatives or analgesics to relieve animals from fear, anxiety, or pain, they attenuate excessive neurohormonal reaction to the noxious stimulus, which contributes to maintaining homeostasis [5,6,7,8]. Α2 -adrenoceptor agonists such as medetomidine, dexmedetomidine, detomidine, xylazine, and clonidine have been reported to decrease tear flow in many animal species, including dogs, cats, horses, pigs, and rats [9,10,11,12,13,14,15,16,17,18]. A decrease in tear flow induced by α2 -adrenoceptor agonists may develop into a serious issue that spoils animal welfare.

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