Abstract

Rats received water or water containing 110 mg of d-amphetamine per liter and ground lab chow or lab chow containing 1 g of propranolol per kg of chow ad libitum for 30 days. Animals receiving no drg and propranolol-fed animals gained weight; those receiving d-amphetamine alone lost weight during the first 14 days then gained weight whereas those receiving both propranolol and d-amphetamine lost weight during the entire 30 days. Steady-state plasma levels of d-amphetamine and the apparent volume of distribution of an intravenous tracer dose of ³H-amphetamine were determined. Steady-state d-am-phetamine levels were higher in animals receiving d-amphetamine and propranolol than in animals receiving only d-amphetamine. This increase in plasma level is due both to a decrease in elimination of d-amphetamine and a decrease in its volume of distribution. Propranolol blocks tolerance to the weight loss produced by d-amphetamine at least in part by increasing the plasma level of d-amphetamine achieved during treatment.