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

Abstract

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...

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

“…Since buspirone had no effect if preceded by NAD-299, it is suggested that reflex modulation by buspirone is mediated by 5-HT 1A receptors. Some of these results have been presented in abstract form Develle and Leblond (2016).…”