Serotonergic agonists facilitate forelimb recovery in rats with cervical spinal cord injury
Serotonergic agents have been shown to improve the recovery of stepping ability in spinalized animals, but not yet of reaching and grasping ability. In the present study we tested whether buspirone, a serotonin 5-HT1A receptor agonist, or fluoxetine, a selective serotonin reuptake inhibitor, would facilitate forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. Following injury, there was a significant decrease in single-pellet reaching and ladder-rung walking performance in all injured rats. From 1-6 weeks post-injury, 31 rats were tested on these tasks with and without Buspirone 1-2 mg/kg; or Fluoxetine 1-5 mg/kg. Buspirone reaching and grasping success rates improved rapidly within 2 weeks post-injury and plateaued over the next 4 weeks of testing. Forelimb performance after buspirone treatment returned to sham levels within 2 weeks of buspirone withdrawal. Fluoxetine treatment resulted in a progressive improvement in performance over 8 weeks, but performance on the ladder test did not change. The improved accuracy of reaching and grasping and the increase in spinal motor evoked potentials demonstrate improved supraspinal-spinal connectivity and within and among spinal sensory-motor networks. Combined these data suggest that buspirone or fluoxetine treatment has therapeutic potential for functional recovery after a cervical spinal cord injury.