Locomotor stimulation by L-dopa: relative importance of noradrenaline receptor activation.
The importance of brain noradrenaline synthesis and receptor activation for the hyperkinesia induced by carbidopa plus L-Dopa in reserpine-treated or normal mice was analyzed in four different models. After pretreatment with reserpine and the monoamine oxidase inhibitor nialamide, the hyperkinesia induced by L-Dopa (25 mg/kg i.p.) was partly mediated via stimulation of noradrenaline receptors since it was significantly antagonized by the noradrenaline receptor-blocking agent phenoxybenzamine. Treatment with reserpine plus L-Dopa (125 mg/kg i.p.) produced an increase in motor activity probably due to stimulation of dopamine receptors since it was not accompanied by an accumulation of noradrenaline and it was not inhibited by phenoxybenzamine. The hyperkinesia following treatment with reserpine and a higher dose of L-Dopa (250 mg/kg i.p.) was probably due to stimulation of both dopamine and noradrenaline receptors since the dopamine-beta-hydroxylase inhibitor FLA-63 partly reduced the effect of L-Dopa. Phenoxybenzamine potentiated the motor stimulation by L-Dopa (125 mg/kg i.p.) in mice not pretreated with reserpine, perhaps depending on a slight enhancement of the net accumulation of brain dopamine. Thus, noradrenaline receptor activation is of importance for the L-Dopa-induced hyperkinesia, at least after high doses or after monoamine oxidase inhibition.
D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013268:Stimulation, Chemical
D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D007980:Levodopa; D009638:Norepinephrine