In vivo evidence for serotonin 5-HT2C receptor-mediated long-lasting excitability of lumbar spinal reflex and its functional interaction with 5-HT1A receptor in the mammalian spinal cord

The purpose of the present study was to investigate the 5-HT2C receptor-mediated effects on the spinal monosynaptic mass reflex activities and also its functional interactions with 5-HT1A receptors in anesthetized, acutely spinalized mammalian adult spinal cord in vivo. Intravenous administration of (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (0.1 mg/kg), an agonist of 5-HT2A/2C receptors, significantly increased the excitability of spinal motoneurons as reflected by an increase in the spinal monosynaptic mass reflex amplitude to 150–200% of the control. 5-HT2A/2C receptor-induced motoneuron excitability was slow, persistent and long-lasting for more than 2 h that was significantly inhibited by 5-HT2C receptor specific antagonist SB 242084 administered 10 min prior to DOI. Simultaneous administration of DOI (0.1 mg/kg, i.v.) along with (±)-8-hydroxy dipropylaminotetraline hydrobromide (8-OH-DPAT) (0.1 mg/kg, i.v.) completely inhibited DOI-induced spinal monosynaptic mass reflex facilitation. In another separate study, administration of 8-OH-DPAT (0.1 mg/kg, i.v.) at the maximum response of DOI also inhibited the motoneuron's excitability; however, the inhibition lasted only for a period of 40–60 min after administration of 8-OH-DPAT, after which the spinal monosynaptic mass reflex amplitude reached its maximum level. These findings suggest that the 5-HT2C receptor is primarily involved in the mediation of the long-lasting excitability of spinal motoneurons and possibly interacts with its functional counterpart, 5-HT1A receptors in the mammalian adult spinal cord.