The Effect of Dopamine and Noradrenaline Antagonists on Amphetamine Induced Locomotor Activity in Mice and Rats

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Abstract
The effect of noradrenaline antagonists, aceperone, phenoxybenzamine and dihydroergotamine and neuroleptic drugs with dopamine receptor blocking properties, i. e. haloperidol, perphenazine, trifluperazine, spiramide and pimozide was tested on the locomotor and rearing activity induced by amphetamine, 2.5 mg/kg, in rats. In general it was found that the neuroleptic drugs in very low doses, haloperidol, 0.10 mg/kg; perphenazine, 0.05 mg/kg; trifluperazine, 0.15 mg/kg; spiramide, 0.05 mg/kg and pimozide, 0.15 mg/kg produced complete inhibition of the amphetamine activities, whereas much higher doses of aceperone, 20 mg/kg and phenoxybenzamine, 20 mg/kg only produced partial antagonism. Dihydroergotamine (20 mg/kg) produced no significant effect on the amphetamine locomotor and rearing activity. In mice trifluperazine (0.2 and 0.4 mg/kg) produced a very marked inhibitory effect, whereas spiramide (0.15 and 0.20 mg/kg) produced a significant but short‐lasting effect on the locomotor activity after 4 and 8 mg/kg d‐amphetamine. Aceperone (5 and 10 mg/kg) and phenoxybenzamine (10 mg/kg) also produced a strong antagonistic effect on the motility. Furthermore α‐methyltyrosine (250 and 350 mg/kg), an inhibitor of the biosynthesis of dopamine and noradrenaline, produced complete inhibition, whereas FLA‐63 (20 and 40 mg/kg), an inhibitor of the formation of noradrenaline produced partial inhibition. In conclusion these results indicate that the locomotor effect in mice and rats after amphetamine is dependent on both dopaminergic and noradrenergic mechanisms. However, dopamine may be regarded as most significant, since the amphetamine motility only seems possible in the presence of functional active dopamine receptors.