Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic reflex via 5-HT1D receptors.
In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT1B receptors mediate the monosynaptic reflex depression induced by exogenously applied 5-HT that was formed from the precursor L-5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by DL-p-chloroamphetamine, on spinal reflexes. DL-p-chloroamphetamine depressed the monosynaptic reflex and increased the polysynaptic reflex. The depletion of 5-HT abolished the monosynaptic reflex depression, but the increase in polysynaptic reflexes was maintained, suggesting that endogenous 5-HT released by DL-p-chloroamphetamine mediates depression of the monosynaptic reflex in the spinal cord. The depression of the monosynaptic reflex was antagonized by GR127935 (N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT1D receptor antagonist) but not by isamoltane (5-HT(1B) receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses monosynaptic reflex transmission via 5-HT1D receptors.
Honda
Motoko
M
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. honda@phar.nagoya-cu.ac.jp
Imaida
Keiko
K
Tanabe
Mitsuo
M
Ono
Hideki
H
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003010:Clorgyline / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology / Q000633:toxicity; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D010133:p-Chloroamphetamine / Q000494:pharmacology / Q000633:toxicity
D001713:Biphenyl Compounds; D008996:Monoamine Oxidase Inhibitors; D010069:Oxadiazoles; D010879:Piperazines; D011725:Pyridines; D044346:Receptor, Serotonin, 5-HT1D; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090701:GR 127935; D012701:Serotonin; D010133:p-Chloroamphetamine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C108532:BRL 15572; D003010:Clorgyline