Differences between (+)- and (-)-amphetamine in effects on locomotor activity and L-dopa potentiating action in mice

Abstract

The L-Dopa-potentiating effects of the two optical isomers of amphetamine, as well as the effects of their own, were investigated in mice, using locomotor activity as test parameter. The study was performed in three steps. First, the time-course were studied for the effects of (+)- and (-)-amphetamine and L-Dopa. Second, dose-response relationships were established for the amphetamine enantiomers. Third, the L-Dopa-potentiating effects, of a few, selected doses of the amphetamine isomers were investigated by establishing dose-response curves for L-Dopa with and without the amphetamines. All animals given L-Dopa were pretreated with an inhibitor of extracerebral aromatic amino acid decarboyxlase. (+)-Amphetamine, 0.5-8 mg/kg, caused a dose-dependent stimulation of locomotoractivity, whereas (-)-amphetamine, 1-4 mg/kg, caused a dose-dependent depression. Doses higher than 8 mg/kg of the laevo-isomer caused stimulation of the activity. (+)-Amphetamine, 0.25 mg/kg, and (-)-amphetamine, 0.5 mg/kg, i.e. doses without any effect on locomotor activity of their own, caused virtually the same shift to the left of the dose-response curve for L-Dopa. (-)-Amphetamine, 4 mg/kg which per se caused depression of locomotor activity, caused a marked potentiation of the L-Dopa-induced stimulation of motor activity. Thus, there does not exist a close correlation between the L-Dopa-potentiating action of the amphetamines and their stimulating properties per se.