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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. [ABSTRACT FROM AUTHOR]

Key points: In newborn rats, L‐DOPA increases the occurrence of air‐stepping activity without affecting movement characteristics.L‐DOPA administration increases the spinal content of dopamine in a dose‐dependent manner.Injection of 5‐HTP increases the spinal serotonin content but does not trigger air‐stepping.5‐HTP counteracts the pro‐locomotor action of L‐DOPA.Less dopamine and serotonin are synthesized when L‐DOPA and 5‐HTP are administered as a cocktail. The catecholamine precursor, L‐3,4‐dihydroxyphenylalanine (L‐DOPA), is a well‐established pharmacological agent for promoting locomotor action in vertebrates, including triggering air‐stepping activities in the neonatal rat. Serotonin is also a well‐known neuromodulator of the rodent spinal locomotor networks. Here, using kinematic analysis, we compared locomotor‐related activities expressed by newborn rats in response to varying doses of L‐DOPA and the serotonin precursor 5‐hydroxytryptophan (5‐HTP) administered separately or in combination. L‐DOPA alone triggered episodes of air‐stepping in a dose‐dependent manner (25–100 mg/kg), notably determining the duration of locomotor episodes, but without affecting step cycle frequency or amplitude. In contrast, 5‐HTP (25–150 mg/kg) was ineffective in instigating air‐stepping, but altered episode durations of L‐DOPA‐induced air‐stepping, and decreased locomotor cycle frequency. High performance liquid chromatography revealed that L‐DOPA, which was undetectable in control conditions, accumulated in a dose‐dependent manner in the lumbar spinal cord 30 min after its administration. This was paralleled by an increase in dopamine levels, whereas the spinal content of noradrenaline and serotonin remained unaffected. In the same way, the spinal levels of serotonin increased in parallel with the dose of 5‐HTP without affecting the levels of dopamine and noradrenaline. When both precursors are administrated, they counteract each other for the production of serotonin and dopamine. Our data thus indicate for the first time that both L‐DOPA and 5‐HTP exert opposing neuromodulatory actions on air‐stepping behaviour in the developing rat, and we speculate that competition for the production of dopamine and serotonin occurs when they are administered as a cocktail. [ABSTRACT FROM AUTHOR]