Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete Spinal Cord Lesion in Mice

Jeffrey-Gauthier, Renaud; Josset, Nicolas; Bretzner, Frédéric; Leblond, Hugues

doi:10.1089/neu.2017.5476

Cited by 10 publications

(10 citation statements)

References 54 publications

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“…Despite its initial inhibitory effect on the H-reflex shown in the present study, it was shown that buspirone promotes locomotor movements after spinal cord injury. Indeed, in another experiment from our laboratory it was shown that buspirone exerts a considerable acute facilitation of spinally-mediated locomotion in mice after a complete section of the spinal cord (Jeffrey-Gauthier et al,2017). Buspirone was also shown to potentiate locomotion when combined with other treatments (Gerasimenko et al,2015, Ung et al,2012.…”

Section: Reflex Inhibition Concomitant With Excitatory Effect On Locomentioning

confidence: 99%

“…In rodents, serotoninergic (5-HT) drugs are effective in triggering and facilitating locomotion after complete spinal lesion (Schmidt andJordan,2000, Slawinska et al,2014). Recent work in our laboratory has established that treatment with the US Food and Drug Administrationapproved 5-HT1A receptor partial agonist buspirone (Loane and Politis,2012) can initiate locomotion in the hind limbs of adult mice immediately after complete spinal lesion (Jeffrey-Gauthier et al,2017). As drugs with pro-locomotor properties also modify reflex pathways, buspirone may alter reflex excitability in mice after complete spinal lesion.…”

Section: Introductionmentioning

confidence: 99%

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Effect of buspirone on the H-reflex in acute spinal decerebrated mice

Develle¹,

Leblond²

2018

Preprint

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2 KEY POINTS SUMMARY Buspirone, a partial serotoninergic agonist (5HT1A), exerts a considerable acute facilitation of spinally-mediated locomotion after a complete spinal lesion in mice.  Since locomotion is associated with reflex modulation, we focused in this study on the effect of buspirone on H-reflex in acute spinal mice after decerebration and removal of anesthesia.  Buspirone injection resulted in a depression of the H-reflex during the first 20 minutes followed, 40 minutes later, by an increase of the reflex.  The H-reflex increase is not due to a disinhibition since buspirone had no effect on the frequency dependent depression (FDD) of the H-reflex.  The use of a model of adult decerebrate mouse with complete spinal cord injury allows to establish that buspirone has a biphasic effect on the H-reflex and that the inhibitory action on sensory information concurs with an excitatory action on locomotion.3 ABSTRACT Pharmacological treatment facilitating locomotor expression also modulates reflex expression through the re-arrangement of spinal networks. Buspirone, a partial serotonin receptor agonist (5-HT1A), was recently shown to facilitate and even trigger locomotor movements in mice after complete spinal lesion (Tx). Here, we studied its effect on the Hreflex after acute Tx in adult mice. To avoid possible impacts of anesthetics on H-reflex depression, experiments were performed after decerebration in un-anesthetized mice (N=13).The H-reflex in plantar muscles of the hind-paw was recorded after tibial nerve stimulation 2 h after Tx at the 8 th thoracic vertebrae. Average H/M ratio was compared before and every 10 min after buspirone (8 mg/kg, i.p.) for 60 min. Frequency-dependent depression (FDD)of the H-reflex was assessed before and 50 min after buspirone. Before buspirone, a stable H-reflex could be elicited in acute spinal mice and FDD of the H-reflex was observed at 5Hz (68%) and 10Hz (70%) relative to 0.2Hz. After buspirone, the H/M ratio was initially significantly decreased to 69% of pre-treatment. It then increased significantly 30 to 60 min after exposure to buspirone, reaching 170% 60 min after injection. FDD 50 min after buspirone was not significantly different that FDD without treatment. Altogether results suggest that the reported pro-locomotor effect of buspirone occurs at a time where there is a reflex depression followed by a second phase marked by enhancement of reflex excitability, denoting functional inhibitory control. Abbreviations: 5-HT: 5-Hydroxytryptamine; 5-HT1A: 1A subunit in 5-Hydroxytryptamine receptor; 8-OHDPAT: 8-Hydroxy-2-DI-n-Propylamino-Tetraline; CPG Central Pattern Generator; EMG: electromyographic; FDD: Frequency Dependent Depression; GABA: Gamma-Aminobutyric-Acid; TASK-1 acid-sensitiv-K-1; Tx: complete transection. Antri M, Mouffle C, Orsal D, and Barthe J. 5-HT 1A receptors are involved in short-and long-term processes responsible for 5-HT-induced locomotor function recovery in chronic spinal rat. Eur J Neurosci 18: 1963-1972, 2003. Barbeau H and Rossignol S. Re...

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Section: Reflex Inhibition Concomitant With Excitatory Effect On Locomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of buspirone on the H-reflex in acute spinal decerebrated mice

Develle¹,

Leblond²

2018

Preprint

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“…was given in a volume of 0.1 cc of saline (0.9%) in the first group. This dose of buspirone was chosen since it was shown to trigger locomotion (Jeffrey-Gauthier et al, 2018). The second group received the 5-HT 1A antagonist NAD-299 (0.66 mg/kg) (Johansson et al, 1997) 10 min before buspirone treatment.…”

Section: Drug Administrationmentioning

confidence: 99%

“…In rodents, serotoninergic (5-HT) drugs are effective in triggering and facilitating locomotion after complete spinal lesion (Schmidt and Jordan, 2000;Slawinska et al, 2014). Recent work in our laboratory has established that treatment with the US Food and Drug Administration-approved 5-HT 1A receptor partial agonist buspirone (Loane and Politis, 2012) can initiate locomotion in the hind limbs of adult mice immediately after complete spinal lesion (Jeffrey-Gauthier et al, 2018). As drugs with pro-locomotor properties also modify reflex pathways, buspirone may alter reflex excitability in mice after complete spinal lesion.…”

Section: Introductionmentioning

confidence: 99%

“…Here, the main objective is to assess the effect of buspirone, at a dose level that is known to trigger locomotion (Jeffrey-Gauthier et al, 2018), on H-reflex amplitude in adult decerebrated mice after acute spinal cord lesion. This reflex, the electrical analog of the tendon tap reflex, is primarily mediated by monosynaptic pathways (Misiaszek, 2003) and regroup both sensori-and motor systems.…”

Section: Introductionmentioning

confidence: 99%

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Biphasic Effect of Buspirone on the H-Reflex in Acute Spinal Decerebrated Mice

Develle

Leblond

2020

Front. Cell. Neurosci.

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Pharmacological treatment facilitating locomotor expression will also have some effects on reflex expression through the modulation of spinal circuitry. Buspirone, a partial serotonin receptor agonist (5-HT 1A), was recently shown to facilitate and even trigger locomotor movements in mice after complete spinal lesion (Tx). Here, we studied its effect on the H-reflex after acute Tx in adult mice. To avoid possible impacts of anesthetics on H-reflex depression, experiments were performed after decerebration in un-anesthetized mice (N = 20). The H-reflex in plantar muscles of the hind paw was recorded after tibial nerve stimulation 2 h after Tx at the 8th thoracic vertebrae and was compared before and every 10 min after buspirone (8 mg/kg, i.p.) for 60 min (N = 8). Frequency-dependent depression (FDD) of the H-reflex was assessed before and 60 min after buspirone. Before buspirone, a stable H-reflex could be elicited in acute spinal mice and FDD of the H-reflex was observed at 5 and 10 Hz relative to 0.2 Hz, FDD was still present 60 min after buspirone. Early after buspirone, the H-reflex was significantly decreased to 69% of pre-treatment, it then increased significantly 30-60 min after treatment, reaching 170% 60 min after injection. This effect was not observed in a control group (saline, N = 5) and was blocked when a 5-HT 1A antagonist (NAD-299) was administered with buspirone (N = 7). Altogether results suggest that the reported pro-locomotor effect of buspirone occurs at a time where there is a 5-HT 1A receptors mediated reflex depression followed by a second phase marked by enhancement of reflex excitability.

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Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury

et al. 2021

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Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT 1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.

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Facilitation of Locomotor Spinal Networks Activity by Buspirone after a Complete Spinal Cord Lesion in Mice

Cited by 10 publications

References 54 publications

Effect of buspirone on the H-reflex in acute spinal decerebrated mice

Effect of buspirone on the H-reflex in acute spinal decerebrated mice

Biphasic Effect of Buspirone on the H-Reflex in Acute Spinal Decerebrated Mice

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury

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