Serotonin 1A Receptor Pharmacotherapy and Neuroplasticity in Spinal Cord Injury

Spinal cord injury is associated with damage in descending and ascending pathways between brainstem/cortex and spinal neurons, leading to loss in sensory-motor functions. This leads not only to locomotor reduction but also to important respiratory impairments, both reducing cardiorespiratory engagement, and increasing cardiovascular risk and mortality. Moreover, individuals with high-level injuries suffer from sleep-disordered breathing in a greater proportion than the general population. Although no current treatments exist to restore motor function in spinal cord injury (SCI), serotoninergic (5-HT) 1A receptor agonists appear as pharmacologic neuromodulators that could be important players in inducing functional improvements by increasing the activation of spared motoneurons. Indeed, single therapies of serotoninergic 1A (5-HT(1A)) agonists allow for acute and temporary recovery of locomotor function. Moreover, the 5-HT(1A) agonist could be even more promising when combined with other pharmacotherapies, exercise training, and/or spinal stimulation, rather than administered alone. In this review, we discuss previous and emerging evidence showing the value of the 5HT(1A) receptor agonist therapies for motor and respiratory limitations in SCI. Moreover, we provide mechanistic hypotheses and clinical impact for the potential benefit of 5-HT(1A) agonist pharmacology in inducing neuroplasticity and improving locomotor and respiratory functions in SCI.