Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior

Abstract

The hypothesis that N-methyl-D-aspartate (NMDA) receptors mediate initiation of lasting behavioral changes induced by the anxiogenic β-carboline, FG-7142, was supported in this study. Behavioral changes normally induced by FG-7142 were blocked when the competitive NMDA receptor blocker, 7-amino-phophono-heptanoic acid, was given prior to administration of FG-7142. When cats were subsequently given FG-7142 alone, the drug produced lasting behavioral changes like those reported previously. Flumazenil, a benzodiazepine receptor antagonist, reversed an increase in defensiveness produced by FG-7142 alone, replicating previous findings. The data are consistent with the hypothesis that NMDA-dependent long-term potentiation in limbic pathways subserving defensive response to threat mediates lasting increases in defensiveness produced by FG-7142.