THE EFFECT OF SOME SEDATING AGENTS ON CALORIGENESIS AND ITS RESPONSES TO 2,4-DINITROPHENOL AND l-THYROXINE IN RATS

¹ The Departments of Internal Medicine and Biological Chemistry, and the Kresge Radio-Isotope Unit, The University of Michigan Medical School, Ann Arbor, Michigan

A sedating agent was sought which would eliminate spontaneous activity in rats without otherwise perturbing oxidative metabolism as measured by the metabolic rate (O₂ consumption). The criteria were that it be effective long enough to permit studies of calorigenesis over a period of two hours, and that it leave unaltered the separate and combined calorigenic effects of 2,4-dinitrophenol and l-thyroxine. Sodium pentobarbital (40 µg/g s.c.) and urethane (1250 µg/g s.c.) did not satisfy these criteria; pretreatment with pentobarbital lowered the initial metabolic rate 34%, accentuated the calorigenic response to l-thyroxine, and resulted in a 50% mortality; pretreatment with urethane depressed the metabolic rate 16%, apparently abolished l-thyroxine-induced calorigenesis, and made dinitrophenol lethal in 40% of the animals. Diazepam (40 µg/g s.c., injected as a 10 mg/ml solution in 30% dimethyl sulfoxide, 45% propylene glycol, 10% ethanol and 15% water) lowered the metabolic rate 10% (as is found with sleep) and did not interfere with dinitrophenol- and l-thyroxine-induced calorigenesis. The measurements of metabolic rates alter pretreatment with diazepam were more precise, due to the elimination of spontaneous movements.