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

Abstract

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.

Serotonin 1A Receptor Pharmacotherapy and Neuroplasticity in Spinal Cord Injury

“…Moreover, it is likely that locomotor improvements are associated with improved motoneuron reflex excitability, as suggested by Develle and Leblond. These authors showed that the same single dose of Buspirone could increase frequency-dependent depression of the H-reflex as compared with saline injection [28] in mice after T8 complete spinal lesion. Moreover, Jin et al [29] showed that the same 5-HT 1A agonist can improve forelimb locomotion by increasing reaching and grasping accuracy as early as 2 weeks post C4 injury in adult female rats [29] using a lower dose of Buspirone (1-2 mg/kg/day, i.p.).…”