Antidepressant-like effects of a partial agonist at strychnine-insensitive glycine receptors and a competitive NMDA receptor antagonist.
Using the forced swimming test in rats (Porsolt test), we examined the antidepressant-like activity of 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at strychnine-insensitive glycine receptors associated with the N-methyl-D-aspartate (NMDA) receptor complex, and of DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), a competitive NMDA receptor antagonist, after their intraperitoneal (i.p.) and intrahippocampal (i.hp.) administration. ACPC (200-400 mg/kg) and CGP 37849 (0.625-5 mg/kg), administered i.p., produced a dose-dependent and significant reduction of the immobility time in the forced swimming test. A similar effect was also observed in i.hp. administration of ACPC (10 and 30 micrograms) and CGP 37849 (0.03 and 0.1 micrograms). Imipramine, used as a reference drug, significantly shortened the immobility time after both i.p. (30 and 40 mg/kg) and i.hp (0.1 and 0.3 micrograms) administration. The compounds studied, administered in doses effective in the forced swimming test, did not change the exploratory activity of the rats, evaluated by an open field test. The present results indicate that, like imipramine, ACPC and CGP 37849 exhibit an antidepressant-like activity in the forced swimming test in rats; moreover, they seem to show the hippocampus may be one of the neuroanatomical sites involved in this effect.
Przegaliński
E
E
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Tatarczyńska
E
E
Dereń-Wesołek
A
A
Chojnacka-Wojcik
E
E
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000928:Antidepressive 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