Histamine H₃ Receptors Expressed in Ventral Horns Modulate Spinal Motor Output

Motoneuron activity is modulated by histamine receptors. While H₁ and H₂ receptors have been widely explored, H₃ histamine receptors (H₃Rs) have not been sufficiently characterized. This paper targets the effects of the selective activation of H₃Rs and their expression on the membranes of large ventral horn cells. The application of selective pharmacological agents to spinal cords isolated from neonatal rats was used to identify the presence of functional H₃Rs on the membrane of physiologically identified lumbar motoneurons. Intra and extracellular recordings revealed that H₃R agonist, α-methylhistamine, depolarized both single motoneurons and ventral roots, even in the presence of tetrodotoxin, an effect prevented by H₃R antagonist, thioperamide. Finally, immunohistochemistry located the expression of H₃Rs on a subpopulation of large cells in lamina IX. This study identifies H₃Rs as a new exploitable pharmacological target against motor disturbances.