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Intranasal Midazolam Effective Dose 50 and Its Effect on Circulating Corticosterone Levels in Zebra Finches

Pathak D, Willis E, Grindstaff J, Pypedop B, Brandão J

From the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, 2065 W. Farm Rd., Stillwater OK 74074, USA (Pathak, Willis, Brandão), Department of Integrative Biology, Oklahoma State University, 501 Life Sciences West, Stillwater, OK 74078, USA (Grindstaff), Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA (Pypendop).

Abstract

Sedation in birds is important for safe handling and minimizing stress. Intranasal (IN) midazolam is commonly used but the minimum effective dose in zebra finches (Taeneopygia guttata) has not been determined. It has been previously suggested that 13 mg/kg IN midazolam1 caused a relative increase in circulating corticosterone (cCORT) when compared to a placebo.2 We hypothesize that high dose of midazolam may induce the release of cCORT. This study had two phases. Phase 1’s objective was to determine the effective dose for 50% of the population (ED50) of IN midazolam using the Dixon Up-and-Down method.3 Each animal received a variable dose based on the response (sedation/no sedation) of the previous animal. A total of 14 birds were used and the ED50 was calculated as 1.67 mg/kg. Phase 2’s objective was to determine the effects of high dose (13 mg/kg, n=9), ED50 (1.7 mg/kg, n=9), and saline (n=9) on cCORT. The study was a masked, randomized, control trial with the same treatment volumes/group. Blood samples were collected at T0 min, treatments were administered, animals were placed in a cloth bag for 20 min, and blood samples were again collected at T20 min. Preliminary results revealed a similar relative increase of cCORT (~4- to 5-fold) following ED50 and high dose midazolam administration, but a lower relative increase (~2-fold) post-saline administration. This study found that the ED50 of IN midazolam is much lower than previously suggested, and that IN midazolam, independent of dose, causes a higher relative increase in cCORT than saline.   

1 - Bigham, A. S., and A. K. Zamani Moghaddam. "Finch (Taeneopygia guttata) sedation with intranasal administration of diazepam, midazolam or xylazine." Journal of veterinary pharmacology and therapeutics 36.1 (2013): 102-104.

2 - Schmidt L, Grindstaff J, Brass K, Womble W, Maranville R, Pathak D, Di Girolamo N, Brandão J (2020) “The effect of intranasal midazolam on corticosterone levels in zebra finches (Taeniopygia guttata)” AAV Avian Medicine Virtual 2020

3 - Dixon, W. J. "The up-and-down method for small samples." Journal of the American Statistical Association 60.312 (1965): 967-978.