Divergent modulation of clinical measures of volitional and reflexive motor behaviors following serotonergic medications in human incomplete spinal cord injury

An incomplete spinal cord injury (SCI) results in profound impairments in volitional strength and reflex excitability, which contribute to loss of function. Human and animal models suggest that disruption of monoaminergic input, particularly serotonin (5HT), from supraspinal centers contributes this impaired motor function following SCI. In the present study, we investigated the effects of 5HT medications on motor function in individuals with chronic (> 1 yr) SCI. Clinical measures of strength, spasticity/spasms, and walking ability were assessed on 12 individuals with chronic incomplete SCI following acute administration of either 8 mg cyproheptadine, a 5HT antagonist, or 10 mg escitalopram, a selective 5HT reuptake inhibitor (SSRI), in a double-blinded, randomized, crossover fashion. Results indicate that 5HT medications modulate both volitional and reflexive behaviors with little change in walking performance; 5HT antagonist medications depressed clinical measures of strength and spasticity/spasms whereas SSRIs augmented both strength and spasticity/spasms. These changes are consistent with the dysregulation of 5HT-sensitive spinal neurons following SCI. This understanding may augment clinicians’ awareness of the motor consequences of 5HT medications.