title: Endogenously released 5-HT inhibits A and C fiber-evoked synaptic transmission in the rat spinal cord by the facilitation of GABA/glycine and 5-HT release via 5-HT(2A) and 5-HT(3) receptors.
abstract: Serotonin (5-HT) released from descending fibers plays important roles in spinal functions such as locomotion and nociception. 5-HT2A and 5-HT3 receptors are suggested to contribute to spinal antinociception, although their activation also contributes to neuronal excitation. In the neonatal spinal cord, DL-p-chloroamphetamine (pCA), a 5-HT releaser, inhibited both A fiber-evoked monosynaptic reflex potential (MSR) and C fiber-evoked slow ventral root potential (sVRP). The pCA-mediated inhibition was reversed by ketanserin (a 5-HT2A receptor antagonist) and tropisetron (a 5-HT3 receptor antagonist). Bath-applied 5-HT also inhibited MSR and sVRP; in this case, the actions of 5-HT were antagonized by ketanserin, but not by tropisetron. The pCA-evoked inhibition of sVRP was reduced by bicuculline (a GABAA receptor antagonist) and strychnine (a glycine receptor antagonist). Furthermore, ketanserin inhibited the pCA-evoked release of gamma-aminobutyric acid (GABA) and glycine, while tropisetron inhibited the pCA-evoked release of 5-HT. These results suggest that 5-HT released by pCA activates 5-HT2A receptors, which in turn stimulates the release of GABA/glycine and thereby blocks the spinal nociceptive pathway. 5-HT3 receptors may be involved in the facilitation of 5-HT release via a positive feedback process.
authors: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors: Takeyuki
authors: T
authors: Iwasaki
authors: Ken-ichi
authors: K
authors: Otsuguro
authors: Takeshi
authors: T
authors: Kobayashi
authors: Toshio
authors: T
authors: Ohta
authors: Shigeo
authors: S
authors: Ito
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D005998:Glycine