Medetomidine has been reported to decrease tear flow significantly in dogs, cats, and pigs when used as a sedative or analgesic; however, there are no such reports when it comes to rats. The present study aimed to investigate the effect of medetomidine on tear flow in rats. Medetomidine in doses of 50, 100, or 200 µg/kg or a physiological saline solution as the control, were administered intramuscularly to male Slc:Wistar/ST rats. After the administration of medetomidine, tear flow in both eyes was measured using a phenol red thread tear test. The area under the curve (AUC) of phenol red thread test values from baseline to 8 h was calculated. Data were plotted against the dose of medetomidine and simple linear regression analysis was performed. The effect of the drug on phenol red thread test values was considered dose-related when linear analysis yielded a significant relationship. In all medetomidine-treated groups, tear flow decreased significantly in both eyes after administration, while no significant changes were observed in either eye in the control group. The AUC values from baseline to 8 h after administration in groups treated with 100 and 200 µg/kg of medetomidine were significantly lower in both the left and right eyes compared to the control group. The linear regression of the AUC values was significant for both eyes. Our results indicated that the intramuscular administration of medetomidine in rats decreased tear flow significantly in a dose-dependent manner.

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.