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.