Stress-induced sensitization and facilitated learning require NMDA receptor activation.

Exposure to an inescapable stressor facilitates acquisition of a classically-conditioned eyeblink response in the freely-moving rat. Here, we tested the hypothesis that the facilitation is mediated via activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor. Rats were injected with the competitive NMDA antagonist CGP-37849 (5 mg kg-1) or vehicle 2 h prior to exposure to restraint and 90, 1 mA, 1 s tail shocks. In contrast to the dramatic facilitation exhibited in stressed rats injected with the vehicle, rats whose NMDA receptors were blocked during exposure to the stressor did not exhibit any facilitation 24 h later. The antagonist alone had no effect on learning. These results demonstrate that the stress-induced facilitation of classical conditioning is dependent on NMDA receptor activation and support the hypothesis that stress is inducing a phenomenon similar in mechanism to that of long-term potentiation (LTP).