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

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