The respiratory neural network is flexible and can undergo neuronal plasticity. Recent work suggests that neurotrophins and their high-affinity tyrosine kinase (Trk) receptors are involved in mediating plasticity of respiratory motor output elicited by intermittent hypoxia. We aimed to determine whether Trk receptor activation is required for plasticity of upper airway motor outflow induced by repeated obstructive apneas that mimic those experienced in obstructive sleep apnea (OSA). We show that Trk receptor inhibition on hypoglossal motor neurons prevents long-term enhancement of genioglossus muscle tone triggered by repeated airway obstructions in rats. Our result suggests that plasticity of upper airway motor outflow requires a functional neurotrophic signaling cascade. Triggering motor plasticity of upper airways via pharmacological mechanisms could be a potentially useful strategy for improving airway patency in OSA.