Differential catecholamine uptake inhibition as a possible mode of action of D-amphetamine induced locomotor activity

A determination was made of the roles played by the selective uptake inhibition versus release of dopamine (DA) or norepinephrine (NE) ex vivo in either the striatum or cerebral cortex in mediating d-amphetamine induced locomotor activity (AILA). Desmethylimipramine (DMI) and/or d-amphetamine variously effected the uptake of DA and NE in both regions in terms of the absolute amount of uptake inhibition elicited by each drug separately or by the two drugs administered concomitantly. However, none of the drug treatments produced a selective inhibition of DA or NE uptake in either the striatum or cerebral cortex. On the other hand, a selective inhibition of central DA release by γ-hydroxybutyrate markedly inhibited AILA. These results suggest that amphetamine induced locomotor activity is not likely mediated by a preferential effect on DA or NE uptake. It is far more probable that AILA is induced by a stimulation of central DA release.