5-HT₂ antagonism indirectly increases motor unit discharge rate and cervicomedullary motor evoked potential amplitude...

Spinal motoneurone excitability is heavily regulated by serotonin via somatodendritic 5-HT₂ receptors. However, the effects of these receptors on the excitability of motoneurones in the upper limb are not clearly understood. Therefore, the purpose of this study was to assess the effects of 5-HT₂ antagonism on motor unit discharge characteristics of the biceps brachii and evoked responses to cervicomedullary stimulation. Twelve healthy individuals (aged 24 ± 3 years) participated in this double-blind, placebo-controlled, two-way crossover trial and were administered the 5-HT₂ antagonist cyproheptadine. high-density surface EMG (HDsEMG) was used to examine motor unit activity in the biceps brachii during trapezoidal contractions of 10%, 20% and 30% maximal voluntary contraction (MVC). Cervicomedullary stimulation was used to produce small and large cervicomedullary motor evoked potentials (CMEPs) in the elbow flexors during these submaximal contractions. Cyproheptadine reduced maximal elbow flexion torque (∼5%, P = 0.003), and increased EMG amplitude (∼2%, P = 0.037), motor unit discharge rates (∼1.5 pulses/s, P = 0.001) and CMEP amplitude from low (∼25%, P = 0.002) and high (∼15%, P = 0.026) intensity stimulation during submaximal contractions. This is the first study to examine the effects of 5-HT₂ antagonism on motoneurone excitability using both HDsEMG and cervicomedullary stimulation in a single experiment. The results of this study provide novel evidence that 5-HT₂ receptor antagonism increases both motor unit discharge rates and CMEP amplitude during elbow flexions when torque targets remain unchanged from baseline. KEY POINTS: Animal models have revealed that serotonin can heavily regulate motoneurone gain via 5-HT₂ receptors. Recently, it has been revealed that 5-HT₂ receptors can modulate motor unit firing characteristics in humans. However, the effect of these receptors on motoneurone excitability of the upper limb is not clearly understood. This study paired high-density surface EMG with cervicomedullary stimulation to provide a novel insight to the effects of 5-HT₂ antagonism on motoneurone excitability. 5-HT₂ antagonism reduced maximal elbow flexor torque, and increased motor unit discharge rates and cervicomedullary motor evoked potential amplitudes during submaximal contractions. These findings suggest that compensatory voluntary drive is required to achieve the same torque level with 5-HT₂ receptor antagonism, indirectly enhancing motoneurone activity and excitability of the motoneurone pool.