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 (A CPC), a partial agonist at strychnine-insensitive glycine receptors as sociated 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 c ompetitive NMDA receptor antagonist, after their intraperitoneal (i.p. ) and intrahippocampal (i.hp.) administration. ACPC (200-400 mg/kg) an d CGP 37849 (0.625-5 mg/kg), administered i.p., produced a dose-depend ent and significant reduction of the immobility time in the forced swi mming test. A similar effect was also observed after i.hp. administrat ion of ACPC (10 and 30 mu g) and CGP 37849 (0.03 and 0.1 mu g). Imipra mine, 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 mu g) a dministration. The compounds studied, administered in doses effective in the forced swimming test, did not change the exploratory activity o f the rats, evaluated by an open field test. The present results indic ate that, like imipramine, ACPC and CGP 37849 exhibit an antidepressan t-like activity in the forced swimming test in rats; moreover, they se em to show that the hippocampus may be one of the neuroanatomical site s involved in this effect. (C) 1997 Elsevier Science Ltd.