Paradoxical effects of d-amphetamine upon seizure susceptibility in 2 selectively bred lines of mice

The ontogeny and substrates of amphetamine-induced changes in flurothyl-induced myoclonic and clonic seizure thresholds were investigated in 2 selectively bred lines of mice. The long-sleep mice exhibited dose-dependent increases in myoclonic and clonic susceptibility following amphetamine, irrespective of age. The noradrenergic agonist clonidine and the dopaminergic agonist apomorphine produced increases in susceptibility comparable to those seen with amphetamine. The short-sleep mice, however, exhibited a dichotomous myoclonic response to amphetamine that was age-dependent. Between 15 and 35 days of age amphetamine decreased seizure susceptibility whereas increases in susceptibility were noted at later ages. With the exception of 80 days, amphetamine did not affect clonic thresholds. In respect to myoclonus, clonidine persisted in producing effects similar to those seen in the long-sleep mice whereas apomorphine exhibited the same ontogenetic alteration in effect seen with amphetamine. These results confirm that the short-sleep mice might be a naturally occurring animal model of preadolescent hyperkinesis. Furthermore, the neuropharmacological tests demonstrate that the paradoxical response to amphetamine in the young short-sleep mice is mediated via a dopaminergic mechanism that must undergo dramatic change during ontogeny.