Tolerance to amphetamine in two species (rat and guinea pig) that metabolize it differently.

It has been proposed that p-hydroxynorephedrine, a metabolite of amphetamine, is responsible for the tolerance that occurs to this drug. To test this idea, the development of tolerance to amphetamine has been examined in two species, the rat and the guinea pig, the former of which produces p-hydroxynorephedrine from amphetamine while the latter does not. In both species, tolerance develops to the anorectic and hyperthermic actions of amphetamine, and similar changes in the pattern of behavioural stimulation are seen.