Effects of Strychnine-Insensitive Glycine Receptor Ligands in Rats Discriminating Dizocilpine or Phencyclidine from Saline

摘要: Several pharmacologically distinct sites are known to modulate the N-methyl-d-aspartate (NMDA) receptor/ion complex, including a site within ion channel which binds uncompetitive antagonists like phencyclidine (PCP) or dizocilpine. Glycine acts as co-agonist for activation of NMDA receptor complex through strychnine-insensitive receptor, is potential target novel therapeutic agents ( e.g. , anticonvulsants, antidepressants). We evaluated behavioral effects glycine ligands in rats trained discriminate either dizocilpine PCP from saline, predict whether might induce undesirable PCP-like subjective humans. Dizocilpine ([+]-MK-801), (−)-MK-801 and produced dose-dependent substitution these with potencies accord affinity. Pentobarbital drugs acting at other competitive (NPC 12626 LY 274614) polyamine antagonist, ifenprodil, did not substitute PCP. In contrast PCP, none substituted. Neither full agonist, glycine; partial agonists, 1-amino-1-cyclopropanecarboxylic acid,d-cycloserine (+)-3-amino-1-hydroxypyrrolid-2-one; nor antagonists, 7-chloro 5,7-dichlorokynurenic acid, mimicked discriminative stimulus Further, co-administration acid significantly enhance Intracerebroventricular administration ofd-serine, selective agonist neither blocked These data suggest that functional may be devoid side characteristic ligands.