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  • Title: Noradrenaline synthesis from L-DOPA in rodents and its relationship to motor activity.
    Author: Dolphin A, Jenner P, Marsden CD.
    Journal: Pharmacol Biochem Behav; 1976 Oct; 5(4):431-9. PubMed ID: 1005491.
    Abstract:
    Evidence has been obtained for an increase in noradrenaline (NA) turnover after administration of L0DOPA to rodents. Normal mice, and those pre-treated with either reserpine or alpha-methyl-p-tyrosine (AMPT) were given L-DOPA (200 mg/kg) plus MK 486 (alpha-methyldopahydrazine; 25 mg/kg). In all cases L-DOPA produced a rise in cerebral dopamine (DA) levels. Cerebral NA levels were increased by L-DOPA in reserpinised and AMPT-treated mice. The same dose of L-DOPA produced no change in NA in normal mice, although pre-treatment with the monoamine oxidase inhibitor pargyline (200 mg/kg) resulted in a greater rise in NA 1 hr after L-DOPA compared to animals receiving pargyline alone. This evidence suggests that NA is synthesized from- L-DOPA in all these situations. But whole brain 3-methoxy-4-hydroxyphenylglocol sulphate (MOPEG-SO4), a major metabolite of NA, measured after administration of the same dose of L-DOPA plus MK 486, was unaltered in normal and AMPT-treated rats, and was significantly decreased in reserpinised rats. However, an elevation of whole brain MOPEG-SO4 was found in reserpinised and AMPT-treated rats after a lower dose of L-DOPA (50 mg/kg). This discrepancy may be explained by high doses of L-DOPA causing inhibiton of catechol-O-methyl transferase (COMT), which is suggested by the observation that the forebrain homovanillic acid (HVA): 3,4-dihydroxyphenylacetic acid (DOPAC) ratio was significantly lower after the high dose of L-DOPA than in untreated mice. Such an inhibition would prevent formation of MOPEG-SO4. Pretreatment with dopamine-beta-hydroxylase inhibitor FLA (63(bis-(1-methyl-4-monopiperazinyl-thiocarbonyl)disulphide) prevented the increase in NA And MOPEG-SO4 formation observed following L-DOPA induced motor activity in these groups of animals suggesting the involvement of NA in the production of such behaviour.
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