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 present study we examined the anxiolytic-like activity of DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist and 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at strychnine-insensitive glycine receptors associated with the NMDA receptor complex, after their intraperitoneal (IP) and intrahippocampal (IHP) administration. CGP 37849, administered in doses of 1.25-5 mg/kg IP, produced an anticonflict effect in a dose-dependent manner, but was inactive when injected in doses 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 impairment. On the other hand, ACPC exhibited an anxiolytic-like activity after both IP (100-200 mg/kg) and IHP (3-30 mu g) administration. These results, as well as the literature data on the lack of motor-impairing effects of ACPC, indicate that the latter drug seems to be more advantageous than CGP 37849 as a potential therapeutic agent in the treatment of anxiety disorders. Furthermore, they also show that the hippocampus may be one of the neuroanatomical sites of the anxiolytic-like effect of ACPC, but not of CGP 37849.