Antidepressant-like Effects of a Partial Agonist at Strychnine-insensitive Glycine Receptors and a Competitive NMDA Receptor Antagonist

Abstract

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 antagonists, 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 after i.hp. administration of ACPC (10 and 30 μg) and CGP 37849 (0.03 and 0.1 μg). 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 μg) 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 that the hippocampus may be one of the neuroanatomical sites involved in this effect. © 1997 Elsevier Science Ltd. All rights reserved.