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Inescapable, but not escapable, stress inhibits the induction of Long Term Potentiation (LTP) in the CA₁ region of hippocampus, a process that is dependent upon activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Since inescapable stress also produces a syndrome of behavioral depression sensitive to clinically effective antidepressants, we examined the actions of functional antagonists at the NMDA receptor complex in animal models commonly used to evaluate potential antidepressants. A competitive NMDA antagonist (2-amino-7-phosphonoheptanoic acid [AP-7]), a non-competitive NMDA antagonist (Dizolcipine [MK-801]), and a partial agonist at strychnine-insensitive glycine receptors (1-aminocylopropanecarboxylic acid [ACPC]) mimicked the effects of clinically effective antidepressants in these models. These findings indicate that the NMDA receptor complex may be involved in …