Stress produced by gavage administration in the rat

This research project examined the relationship between gavage administrati on of various vehicles and induction of the stress response, as defined by increased plasma corticosterone levels, in the rat. In addition, we assesse d elicitation of clinical signs of distress and aspiration leading to airwa y/pulmonary changes. We studied various vehicles used in toxicology studies , including water, corn oil, and 1% methylcellulose/0.2% Tween 80, Male CD( R) rats received a single gavage administration of vehicle, blood was colle cted 1 h after dosing for measurement of plasma corticosterone, and necrops ies were performed 4 h after dosing. Gavage administration of corn oil at g reater than or equal to 20 mL/kg, but not 1% methylcellulose/0.2% Tween 80 or water, induced a stress response in a volume-dependent fashion, resultin g in elevated plasma corticosterone levels. This response was not due to as piration, which occurred after administration of greater than or equal to 2 0 mL/kg of water or greater than or equal to methylcellulose/0.2% Tween 80 but not corn oil. ridministration of corn oil at 40 mL/kg resulted in plasm a corticosterone levels that were elevated for 4 h, The stress response pro duced by corn oil was not unique to this vehicle but also occurred after ga vage administration of sesame, soybean, and peanut oils. Our data indicate that gavage dosing of lipid vehicles induces activation of the stress respo nse, as indicated by increased adrenal output of corticosterone, in a volum e-dependent fashion. In conclusion, gavage administration of various vehicl es can result in aspiration, pulmonary injury, and/or elicitation of a stre ss response in a vehicle- and dose volume-dependent fashion. The results of our project suggest that dose volumes for gavage administration in the rat generally should not exceed 10 mL/kg.