Novelty exploration elicits a reversal of acute stress‐induced modulation of hippocampal synaptic plasticity in the rat

Acute behavioural stress has been recognized as a strong influence on the inducibility of hippocampal long‐term synaptic plasticity. We have reported previously that in adult male rats, acute behavioural stress impairs long‐term potentiation (LTP) but enhances long‐term depression (LTD) in the hippocampal CA1 region. In this study we report that the effects of stress on LTP and LTD were reversed when animals were introduced into a novel ‘stimulus‐rich’ environment immediately after the stress. Novelty exploration‐induced reversal of stress effects was prevented when the animals were given the NMDA receptor antagonist d ‐(−)‐2‐amino‐5‐phosphonopentanoic acid, the cholinergic antagonist atropine and the protein phosphatase (PP) 2B inhibitors cyclosporin A and cypermethrin, but not the α 1 ‐adrenergic antagonist prazosin, the β‐adrenergic antagonist propranolol or the PP1/2A inhibitor okadaic acid, respectively before being subjected to the novel environment. In addition, the ability of novelty exploration to reverse the stress effects was mimicked by a direct application of the cholinergic agonist carbachol. Exposure to the novel environment following stress was accompanied by the activation of both PP2B and striatal‐enriched tyrosine phosphatase (STEP). Taken together, these findings suggest that the activation of the cholinergic system and, in turn, the triggering of an NMDA receptor‐mediated activation of PP2B to increase STEP activity appear to mediate the novelty exploration‐induced reversal of stress‐related modulation of hippocampal long‐term synaptic plasticity.