A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.
Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuously for 5h after treatment, and feces collected 6-10h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5h, while MAP returned to normal within 2h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2-5h post dosing. MAP and heart rate did not differ 24h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic-pituitary-adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage.
Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. mwalker@salud.unm.edu
Mary K
MK
Walker
Jason R
JR
Boberg
Mary T
MT
Walsh
Valerie
V
Wolf
Alisha
A
Trujillo
Melissa Skelton
MS
Duke
Rupert
R
Palme
Linda A
LA
Felton
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D064420:Drug-Related Side Effects and Adverse Reactions; D006339:Heart Rate / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D013312:Stress, Physiological; D013686:Telemetry / Q000379:methods; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
D004364:Pharmaceutical Preparations