Persistent Inhibition of Hippocampal Long-Term Potentiation In Vivo by Learned Helplessness Stress

The persistent cognitive disruptive effects of stress have been strongly,implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LIP that required voltage-dependent Ca2+ channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LIP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LIP inhibition. Moreover, LIP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress. (C) 2009 Wiley-Liss, Inc.