L‐DOPA and 5‐HTP modulation of air‐stepping in newborn rats

Boulain, Marie; Yuan, Wei; Oueghlani, Zied; Khsime, Inès; Salvi, V.S.; Courtand, Gilles; Halgand, Christophe; Morin, Didier; Deurwaerdère, Philippe De; Barrière, Grégory; Juvin, Laurent

doi:10.1113/jp281983

Cited by 3 publications

(12 citation statements)

References 89 publications

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“…In agreement with our recent work [19], measured L-DOPA, which remained below its detection threshold following saline injection (see above), uniformly accumulated in the cervical and lumbar enlargements 30 min after its administration at the dose of 25 mg/kg (Figure 5, Table 1). It is noteworthy that the tissue levels of L-DOPA measured after 25 mg/kg L-DOPA (Figure 5) are approximately 10 to 20-fold higher compared to the levels measured after nialamide or tolcapone alone (Figure 4A, Table 1).…”

Section: L-dopa At Different Dosessupporting

confidence: 92%

“…In the present work, L-DOPA induced a dose-dependent increase of the number of newborn rats exhibiting air-stepping from 25 to 100 mg/kg. This is consistent with our first evaluation showing that 100% of the cohort exhibited air-stepping at the dose of 50 mg/kg L-DOPA and for prolonged periods of time from 75 mg/kg [19]. A higher dose of L-DOPA (150 mg/kg) did not reveal additional effects compared to those already seen at 100 mg/kg except a slightly higher proportion of quadrupedal stepping and number of hindlimbs steps.…”

Section: Monoamines Contribution To L-dopa Pro-locomotor Actionsupporting

confidence: 91%

“…In reality, it is likely an overestimation because the limit of quantification of L-DOPA in that experiment, due to its time of elution at the end of the solvent front was very low (estimated to be 30-40 pg in a sample). The HPLC conditions were initially satisfying the measurement of tissue L-DOPA in response to L-DOPA injection (very high levels, even after the lower dose of L-DOPA; [19]) but not basal L-DOPA tissue content.…”

Section: Manipulating the Enzymatic Pathways Operating Spinal Monoaminesmentioning

confidence: 98%

“…In our previous study, we showed that L-DOPA administered peripherally was not effective at the dose of 25 mg/kg to trigger air-stepping in the newborn rat. The threshold to trigger the behavior in all animals is around 50 mg/kg, the most robust episodes being obtained at even higher doses (75-100 mg/kg [19]). In a context where one would use L-DOPA administration as a support to facilitate the expression of locomotor activity in pathological contexts, such as following a spinal cord injury, chronic or repeated L-DOPA administration at high dose can be a burden [1].…”

Section: Introductionmentioning

confidence: 96%

“…The newborn rat is an interesting model for addressing the locomotor effects of L-DOPA since its peripheral administration triggers episodes of air-stepping 2 of 24 in a dose-dependent manner [17,18]. Combining kinematic and biochemical approaches, we recently showed that the pro-locomotor action of L-DOPA was paralleled by an accumulation of L-DOPA itself and its by-end product dopamine in the spinal cord [19]. The aromatic amino-acid decarboxylase (AADC), which is responsible for the transformation of L-DOPA into dopamine, is expressed in the spinal cord in the perinatal period [20,21].…”

Section: Introductionmentioning

confidence: 99%

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

Khsime,

Boulain,

Fettah

et al. 2023

IJMS

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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.

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Section: L-dopa At Different Dosessupporting

confidence: 92%

Section: Monoamines Contribution To L-dopa Pro-locomotor Actionsupporting

confidence: 91%

Section: Manipulating the Enzymatic Pathways Operating Spinal Monoaminesmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Khsime,

Boulain,

Fettah

et al. 2023

IJMS

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Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) on rhythmic electrical activity of the lumbosacral spinal cord in cats

Moreno-Castillo,

Guertin,

Manjarrez

2024

Biomedicine & Pharmacotherapy

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Air-stepping in the neonatal mouse: a powerful tool for analyzing early stages of rhythmic limb movement development

Mistretta,

Wood,

English

et al. 2024

Journal of Neurophysiology

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There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study L-DOPA induced air-stepping in mice at postnatal day 7 (P7) and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion, but without constraints imposed by weight-bearing, postural adjustments or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of L-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10, but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages indicating maturation of flexion-extension cycles as the animal starts to walk. Electromyographic recording of TA and LG show alternation, but with more focused activation particularly in the LG from P7 to P10. We discuss similarities with neonatal rat L-DOPA induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and paves the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.

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L‐DOPA and 5‐HTP modulation of air‐stepping in newborn rats

Abstract: support-information-section).

Cited by 3 publications

References 89 publications

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

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

Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) on rhythmic electrical activity of the lumbosacral spinal cord in cats

Air-stepping in the neonatal mouse: a powerful tool for analyzing early stages of rhythmic limb movement development

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