Effects of Serotonergic Activation on Respiratory Motor Recovery following Chronic Cervical Spinal Cord Injury

Abstract

Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in attenuation of the phrenic motor output. It has been shown that activation of serotonergic system can induce partial recovery of phrenic activity after acute C2Hx. The purpose of present study was to examine whether manipulation of the serotonin system can still improve respiratory function during the chronic injury phase. Bilateral diaphragm electromyogram (EMG) and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 weeks post‐C2Hx or C2 laminectomy. A bolus intravenous injection of a serotonin precursor (5‐Hydroxytryptophan; 5‐HTP, 10 mg/kg) or a potent agonist for serotonin 2A receptor agonist (TCB‐2, 0.05 mg/kg) was used to activate serotonergic system. Current results demonstrated that both 5‐HTP and TCB‐2 significantly induced a persistent increase in activity of the diaphragm EMG ipsilateral to the lesion but not contralateral diaphragm in C2Hx animals or bilateral diaphragm in uninjured animals. However, the tidal volume was not changed after administration of 5‐HTP or TCB‐2, indicating the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that activation of the serotonergic system can specifically increase the ipsilateral diaphragmatic motor output, but it is not sufficient to improve respiratory functional recovery following chronic cervical spinal injury.