Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / administration & dosage
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2-Amino-5-phosphonovalerate / pharmacology
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Agmatine / administration & dosage
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Agmatine / pharmacology
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Animals
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Cycloserine / administration & dosage
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Cycloserine / pharmacology*
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Dizocilpine Maleate / administration & dosage
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Dizocilpine Maleate / pharmacology
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Dose-Response Relationship, Drug
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Injections, Spinal
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Ion Channels / metabolism*
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Kynurenic Acid / administration & dosage
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Kynurenic Acid / analogs & derivatives
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Kynurenic Acid / pharmacology
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Mice
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Morphine / pharmacology
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Neurokinin A / administration & dosage
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Neurokinin A / analogs & derivatives
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Neurokinin A / pharmacology
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Nociceptors / drug effects*
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Nociceptors / metabolism
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Nociceptors / physiopathology
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Pain / chemically induced
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Pain / physiopathology
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Pain / prevention & control
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology
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Piperidines / administration & dosage
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Piperidines / pharmacology
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Receptors, Glycine / metabolism*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Receptors, Tachykinin / antagonists & inhibitors
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Receptors, Tachykinin / metabolism
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Substance P / administration & dosage
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Substance P / analogs & derivatives
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Substance P / pharmacology
Substances
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Ion Channels
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Peptide Fragments
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Piperidines
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate
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Receptors, Tachykinin
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substance P (6-11), Phe(7)-His(9)-
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neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-
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Substance P
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Dizocilpine Maleate
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Agmatine
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2-Amino-5-phosphonovalerate
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Morphine
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Neurokinin A
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Cycloserine
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Kynurenic Acid
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ifenprodil
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7-chlorokynurenic acid