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 (i.p.) and intrahippocampal (IHP) administration. CGP 37849, administered in doses of 1.25-5 mg/kg i.p., produced an anticonflict effect in a dose-dependent manner, but was inactive when injected in doses of 0.01-0.1 micrograms IHP. At the same time, when administered in higher doses (10 mg/kg i.p. or 0.3 micrograms IHP), that drug induced motor impairment. On the other hand, ACPC exhibited an anxiolytic-like activity after both i.p. (100-200 mg/kg) and IHP (3-30 micrograms) 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.
Przegaliński
E
E
Institute of Pharmacology, Kraków, Poland.
Tatarczyńska
E
E
Dereń-Wesołek
A
A
Chojnacka-Wójcik
E
E
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists* / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013331:Strychnine / Q000494:pharmacology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; C023863:1-aminocyclopropane-1-carboxylic acid; D015763:2-Amino-5-phosphonovalerate; D013331:Strychnine