Serotonergic Modulation of Spinal Circuitry Restores Motor Function after Chronic Spinal Cord Injury

Abstract

Upper limb motor recovery is a priority for chronic SCI patients to improve functionality and quality of life. Treatment options available for acute SCI provide limited benefit to those with persistent motor symptoms years after injury, creating a need for interventions to target chronic motor damage. Our therapeutic approach utilizes quipazine, a serotonergic agonist, as a chemical neuromodulator to induce plasticity of spared motor pathways in a rat model of chronic SCI. Therapy consisted of quipazine delivery via microinfusion pump and physical training with a forelimb reach-and-grasp task. We found that quipazine administration produced a significant improvement in motor performance over rats receiving physical training alone. These therapeutic gains persisted beyond the period of quipazine administration during a four-week follow up period, producing a long-term improvement in motor performance. Notably, our intervention produced the greatest gains in rats with more severe injuries over those with moderate injuries. When analyzing reach vs. grasp as individual components of total motor performance, quipazine administration produced greater gains in both measures, compared with physical training alone. Our results provide evidence for quipazine administration as a therapeutic intervention to promote long-term motor benefits in chronic SCI. Our data offers support for the role of quipazine as a modulator of the dysregulated serotonergic system in SCI, promoting functional recovery. These findings have implications for the future use of neuromodulator therapy in improving motor performance to address the needs of chronic SCI patients.