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

J Pharmacol Sci. 2007 May;104(1):39-45. doi: 10.1254/jphs.fp0070203. Epub 2007 Apr 24.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / administration & dosage
  • 2-Amino-5-phosphonovalerate / pharmacology
  • Agmatine / administration & dosage
  • Agmatine / pharmacology
  • Animals
  • Cycloserine / administration & dosage
  • Cycloserine / pharmacology*
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology
  • Dose-Response Relationship, Drug
  • Injections, Spinal
  • Ion Channels / metabolism*
  • Kynurenic Acid / administration & dosage
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • Mice
  • Morphine / pharmacology
  • Neurokinin A / administration & dosage
  • Neurokinin A / analogs & derivatives
  • Neurokinin A / pharmacology
  • Nociceptors / drug effects*
  • Nociceptors / metabolism
  • Nociceptors / physiopathology
  • Pain / chemically induced
  • Pain / physiopathology
  • Pain / prevention & control
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • Piperidines / administration & dosage
  • Piperidines / pharmacology
  • Receptors, Glycine / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, Tachykinin / antagonists & inhibitors
  • Receptors, Tachykinin / metabolism
  • Substance P / administration & dosage
  • Substance P / analogs & derivatives
  • Substance P / pharmacology

Substances

  • Ion Channels
  • Peptide Fragments
  • Piperidines
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Tachykinin
  • substance P (6-11), Phe(7)-His(9)-
  • neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-
  • Substance P
  • Dizocilpine Maleate
  • Agmatine
  • 2-Amino-5-phosphonovalerate
  • Morphine
  • Neurokinin A
  • Cycloserine
  • Kynurenic Acid
  • ifenprodil
  • 7-chlorokynurenic acid