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-HT(2C) receptor-mediated effects on the spinal monosynaptic mass reflex activities and also its functional interactions with 5-HT(1A) 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-HT(2A/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-HT(2A/2C) receptor-induced motoneuron excitability was slow, persistent and long-lasting for more than 2h that was significantly inhibited by 5-HT(2C) 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-HT(2C) receptor is primarily involved in the mediation of the long-lasting excitability of spinal motoneurons and possibly interacts with its functional counterpart, 5-HT(1A) receptors in the mammalian adult spinal cord.
Gajendiran
Mahadevan
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12 Ichigaya, Funagawara-machi, Shinjuku-ku, Tokyo 162, Japan. gajendiran.mahadevan@vanderbilt.edu
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D000662:Amphetamines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine