Modification of the L-DOPA reversal of reserpine akinesia by inhibitors of dopamine-beta-hydroxylase.
The effect of the dopamine-beta-hydroxylase inhibitors (DBHI) FLA-63 and U10,157 on the reversal of reserpine akinesia by L-DOPA in mice was investigated both behaviourally and by measurement of the cerebral amines dopamine and noradrenaline. Pretreatment of reserpinised animals with intraperitoneal, but not oral, FLA-63 produced hypermotility in the first hour after L-DOPA administration, compared to animals receiving L-DOPA alone. This enhanced activity was associated with an increase in dopamine, but no significant change in the noradrenaline content of whole brain. Pretreatment with both oral and intraperitoneal FLA-63 caused dose-dependent suppression of locomotor activity in the second and third hours after L-DOPA. This suppression was associated with a significant decrease in brain noradrenaline in the presence of a significant elevation in brain dopamine. Pretreatment of animals with U10,157 produced similar but less marked behavioural responses. The results do not appear to be due to stressful effects of DBHI's, causing release of corticosteroids; neither corticosterone nor beta-methasone had any significant effect on L-DOPA-induced locomotor activity in reserpinised animals, although they did increase spontaneous motor activity in normal animals. The data presented support the concept that both noradrenaline and dopamine are responsible for the gross motor activity induced by L-DOPA in the reserpinised mouse.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010670:Phenylthiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D012110:Reserpine / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D002395:Catecholamines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D007980:Levodopa; D010670:Phenylthiourea; D012110:Reserpine