Limiting Monoamines Degradation Increases L-DOPA Pro-Locomotor Action in Newborn Rats

L-DOPA, the precursor of catecholamines, exerts a pro-locomotor action in several vertebrate species, including newborn rats. Here, we tested the hypothesis that decreasing the degradation of monoamines can promote the pro-locomotor action of a low, subthreshold dose of L-DOPA in five-day-old rats....

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Published inInternational journal of molecular sciences Vol. 24; no. 19; p. 14747
Main Authors Khsime, Inès, Boulain, Marie, Fettah, Abderrahman, Chagraoui, Abdeslam, Courtand, Gilles, De Deurwaerdère, Philippe, Juvin, Laurent, Barrière, Grégory
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2023
MDPI
Subjects
air-stepping
Animals
Catecholamines
Dopamine
L-DOPA
Life Sciences
monoamines
Neurobiology
Neurons and Cognition
newborn rat
Noradrenaline
Oxidases
Phenols
Spinal cord
Tolcapone
France
air-stepping
spinal cord
newborn rat
L-DOPA
monoamines
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Summary:L-DOPA, the precursor of catecholamines, exerts a pro-locomotor action in several vertebrate species, including newborn rats. Here, we tested the hypothesis that decreasing the degradation of monoamines can promote the pro-locomotor action of a low, subthreshold dose of L-DOPA in five-day-old rats. The activity of the degrading pathways involving monoamine oxidases or catechol-O-methyltransferase was impaired by injecting nialamide or tolcapone, respectively. At this early post-natal stage, the capacity of the drugs to trigger locomotion was investigated by monitoring the air-stepping activity expressed by the animals suspended in a harness above the ground. We show that nialamide (100 mg/kg) or tolcapone (100 mg/kg), without effect on their own promotes maximal expression of air-stepping sequences in the presence of a sub-effective dose of L-DOPA (25 mg/kg). Tissue measurements of monoamines (dopamine, noradrenaline, serotonin and some of their metabolites) in the cervical and lumbar spinal cord confirmed the regional efficacy of each inhibitor toward their respective enzyme. Our experiments support the idea that the raise of monoamines boost L-DOPA’s locomotor action. Considering that both inhibitors differently altered the spinal monoamines levels in response to L-DOPA, our data also suggest that maximal locomotor response can be reached with different monoamines environment.
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These authors contributed equally to this work and co-last authors.
These authors contributed equally to this work and co-first authors.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241914747