Excitatory effect of histamine on rat spinal motoneurons by activation of both H₁ and H₂ receptors in vitro

The central histaminergic nervous system, originating from the tuberomammillary nucleus of the hypothalamus, widely innervates almost the whole brain as well as the spinal cord. However, the effect of histamine on spinal motoneurons, the final common path for motor control, is still unknown. By using 8-14-day-old rat spinal slice preparations and intracellular recordings, the effect of histamine on motoneurons in lumbar spinal cord and the underlying mechanisms were studied. Bath application of histamine (30-300 μM) induced a membrane depolarization in the majority of recorded spinal motoneurons (78/90, 86%). Perfusing slices with tetrodotoxin or low-Ca²⁺/high-Mg²⁺ medium did not block the histamine-induced excitation, indicating a direct postsynaptic action of histamine on motoneurons. Separate application of the selective histamine H₁ receptor antagonist mepyramine or the selective histamine H₂ receptor antagonist ranitidine partially suppressed the histamine-induced excitation, whereas a combination of ranitidine and mepyramine totally blocked the excitatory effect of histamine on motoneurons. On the other hand, both the selective histamine H₁ receptor agonist 2-pyridylethylamine and the selective histamine H₂ receptor agonist dimaprit mimicked the excitation of histamine on spinal motoneurons. These agonist-induced excitations were also blocked by mepyramine or ranitidine. Furthermore, histamine affected membrane input resistance and potentiated repetitive firing behavior of spinal motoneurons. These results demonstrate that histamine excites rat spinal motoneurons via the histamine H₁ and H₂ receptors and increases their excitability, suggesting that the hypothalamospinal histaminergic fibers may directly modulate final motor outputs and actively regulate ongoing motor execution andspinal motor reflexes. © 2011 Wiley Periodicals, Inc.