Pharmacological antagonism of facilitatory but not inhibitory effects of serotonin and norepinephrine on excitability of spinal motoneurons

Serotonin (5HT) and norepinephrine (NE) produced long-lasting facilitation of glutamate-evoked activity of spinal motoneurons when applied iontophoretically with small ejection currents into the ventral horn. The facilitation was usually preceded by a brief period of inhibition at the onset of current application to the monoamine-containing barrels. This inhibition did not outlast the current application. Ejection of hydrogen ions produced only inhibition of glutamate-evoked activity with no subsequent facilitation at current offset. The 5HT antagonists, methysergide and metergoline, blocked the facilitation, but not the inhibition of motoneuron excitability caused by 5HT. Similarly, the alpha-adrenergic antagonists, piperoxane and phentolamine, blocked the facilitatory, but not the inhibitory, effects of NE on excitability of motoneurons. Since the inhibitory effects of 5HT and NE could not be blocked with the antagonists used, and since ejection of hydrogen ions also produced inhibition, non-specific causes for the inhibitory effects of 5HT and NE could not be rejected. However, the facilitatory effects of 5HT and NE on excitability of motoneurons were readily blocked by antagonists and were, therefore, attributed to actions on separate 5HT and NE receptors in the ventral horn.