Studies on the mechanisms of tolerance to the anorectic effect of salbutamol in rats.

Two daily injections of 10 mg/kg salbutamol for 6 days caused complete tolerance in rats to the inhibitory effect on food intake measured 19 h after the last injection. Tolerance was not contingent on the time that elapsed between drug injections and eating during repeated treatment ('physiological' tolerance) and was reversible since the effect of salbutamol on food intake was completely reinstated 5 days after drug discontinuation. The anorectic effects of d-amphetamine and d-fenfluramine were not significantly modified in salbutamol tolerant animals, suggesting that the mechanisms involved in the tolerance to the effect of salbutamol are different from those involved in the effect of d-amphetamine and d-fenfluramine to cause depression of food intake in rats.