Intrathecally administered D-cycloserine produces nociceptive behavior through the activation of N-methyl-D-aspartate receptor ion-channel complex acting on the glycine recognition site.
Intrathecal (i.t.) administration of D-cycloserine (100 and 300 fmol), a partial agonist of the glycine recognition site on the N-methyl-D-aspartate (NMDA) receptor ion-channel complex, produced a behavioral response mainly consisting of biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank in mice, which peaked at 5 - 10 min and almost disappeared at 15 min after the injection. The behavior induced by D-cycloserine (300 fmol) was dose-dependently inhibited by an intraperitoneal injection of morphine (0.5-2 mg/kg), suggesting that the behavioral response is related to nociception. The nociceptive behavior was also dose-dependently inhibited by i.t. co-administration of 7-chlorokynurenic acid (0.25-4 nmol), a competitive antagonist of the glycine recognition site on the NMDA receptor ion-channel complex; D-(-)-2-amino-5-phosphonovaleric acid (62.5-500 pmol), a competitive NMDA receptor antagonist; MK-801 (62.5-500 pmol), an NMDA ion-channel blocker; ifenprodil (0.5-8 nmol); arcaine (31-125 pmol); and agmatine (0.1-10 pmol), all being antagonists of the polyamine recognition site on the NMDA receptor ion-channel complex. However, [D-Phe7,D-His9]-substance P(6-11), a specific antagonist for substance P (NK1) receptors, and MEN-10,376, a tachykinin NK2-receptor antagonist, had no effect on D-cycloserine-induced nociceptive behavior. These results in the mouse spinal cord suggest that D-cycloserine-induced nociceptive behavior is mediated through the activation of the NMDA receptor ion-channel complex by acting on the glycine recognition site and that it does not involve the tachykinin receptor mechanism.
Tan-No
Koichi
K
Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan. koichi@tohoku-pharm.ac.jp
Esashi
Akihisa
A
Nakagawasai
Osamu
O
Niijima
Fukie
F
Furuta
Seiichi
S
Sato
Takumi
T
Satoh
Susumu
S
Yasuhara
Hajime
H
Tadano
Takeshi
T
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003523:Cycloserine / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D007473:Ion Channels / Q000378:metabolism*; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D015288:Neurokinin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D018009:Receptors, Glycine / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D007473:Ion Channels; D010446:Peptide Fragments; D010880:Piperidines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D018039:Receptors, Tachykinin; C523357:substance P (6-11), Phe(7)-His(9)-; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D013373:Substance P; D016291:Dizocilpine Maleate; D000376:Agmatine; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; D015288:Neurokinin A; D003523:Cycloserine; D007736:Kynurenic Acid; C010739:ifenprodil; C057013:7-chlorokynurenic acid