Serotonergic depression of spinal monosynaptic transmission is mediated by 5-HT1B receptors.
In the spinal cord, various subtypes of serotonin (5-hydroxytryptamine; 5-HT) receptors are involved in the modulation of motor output. Although the excitatory role of 5-HT(2) receptors is known, the receptor subtypes mediating the inhibitory effect of 5-HT on monosynaptic reflex transmission remain unclear. In this study, segmental spinal reflexes were recorded to examine the receptor subtypes underlying 5-HT-mediated inhibition of monosynaptic reflex transmission in spinalized rats. Under conditions of monoamine oxidase blockade with clorgyline, the 5-HT precursor L-5-hydroxytryptophan depressed the monosynaptic reflex. 3-Hydroxybenzylhydrazine dihydrochloride (NSD-1015), a centrally active decarboxylase inhibitor, abolished this inhibition, confirming that the depression of the monosynaptic reflex by L-5-hydroxytryptophan was due to 5-HT. In the presence of GR127935 or isamoltane, which show high affinity for 5-HT(1B) receptors, L-5-hydroxytryptophan did not suppress the monosynaptic reflex, whereas 5-HT(1A), 5-HT(1D), 5-HT(2) and 5-HT(7) receptor antagonists did not alter the inhibitory effect of L-5-hydroxytryptophan. These results suggest that serotonergic depression of monosynaptic reflex transmission is mediated by 5-HT(1B) receptors.
Honda
Motoko
M
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho, Nagoya 467-8603, Japan. honda@phar.nagoya-cu.ac.jp
Tanabe
Mitsuo
M
Ono
Hideki
H
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D006916:5-Hydroxytryptophan