Acute restraint stress impairs induction of long-term potentiation by activating GSK-3β.

The present study investigated the effect of acute restraint stress on long-term potentiation (LTP) and the underlying mechanism. Induction of Schaffer collateral-CA1 LTP was suppressed in hippocampal slices from mice with 1-h restraint stress. Cell surface localization of the N-methyl-D-aspartate (NMDA) receptor subunits NR1 and NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1 and GluA2 was not affected in the hippocampus from mice with 1-h restraint stress. Phosphorylation of Akt at Ser473, but not at Thr308, and phosphorylation of GSK-3β at Ser9, but not at Tyr216, were significantly inhibited in the hippocampus with 1-h restraint stress. Taken together, the results of the present study show that acute restraint stress impairs induction of LTP by enhancing GSK-3β activity following suppressed Akt activity, without affecting cell surface localization of the NMDA and AMPA receptor subunits.