ANTICONFLICT EFFECTS OF A COMPETITIVE NMDA RECEPTOR ANTAGONIST AND A PARTIAL AGONIST AT STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS

Using the conflict drinking Vogel test in rats as a model, in the pres ent study we examined the anxiolytic-like activity of DL-(E)-2-amino-4 -methyl-5-phosphono-3-pentenoic acid (CGP 37849), a competitive N-meth yl-D-aspartate (NMDA) receptor antagonist and 1-aminocyclopropanecarbo xylic acid (ACPC), a partial agonist at strychnine-insensitive glycine receptors associated with the NMDA receptor complex, after their intr aperitoneal (IP) and intrahippocampal (IHP) administration. CGP 37849, administered in doses of 1.25-5 mg/kg IP, produced an anticonflict ef fect in a dose-dependent manner, but was inactive when injected in dos es of 0.01-0.1 mu g IHP. At the same time, when administered in higher doses (10 mg/kg IP or 0.3 mu g IHP), that drug induced motor impairme nt. On the other hand, ACPC exhibited an anxiolytic-like activity afte r both IP (100-200 mg/kg) and IHP (3-30 mu g) administration. These re sults, as well as the literature data on the lack of motor-impairing e ffects of ACPC, indicate that the latter drug seems to be more advanta geous than CGP 37849 as a potential therapeutic agent in the treatment of anxiety disorders. Furthermore, they also show that the hippocampu s may be one of the neuroanatomical sites of the anxiolytic-like effec t of ACPC, but not of CGP 37849.