Paradoxical effect of amphetamine in an endogenous model of the hyperkinetic syndrome in a hybrid dog: correlation with amphetamine and p-hydroxyamphetamine blood levels.

A telomian-beagle hybrid has been studied as a possible model for the hyperkinetic syndrome in children. Behavior tests showed that hybrids, like children, exhibit hyperactivity, impulsiveness, and impaired learning. Two groups of hybrid could be differentiated; the behaviour of one improved after amphetamine (responders) while that of the other did not (nonresponders). Moreover hybrids were less responsive than beagles to other effects of amphetamine such as stereotyped behaviour and hyperthermia. Measurement of blood levels of amphetamine and its active metabolite p-hydroxyamphetamine (pOA) showed that hybrids form less pOA. We propose that the lesser response of hybrids to toxic effects of amphetamine is due to this difference in amphetamine metabolism. Responders showed higher peak blood levels of amphetamine than nonresponders and their improvement on amphetamine correlated with blood levels of amphetamine. Therefore high levels of amphetamine appear to be necessary for its 'paradoxical' effect in this model. This suggests that amphetamine acts by activating both noradrenergic and dopaminergic neuronal systems in the CNS.