title: Novelty exploration elicits a reversal of acute stress-induced modulation of hippocampal synaptic plasticity in the rat.
abstract: 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 alpha1-adrenergic antagonist prazosin, the beta-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.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan City 701, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005106:Exploratory Behavior; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D065095:Calcineurin Inhibitors; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; D048049:Extracellular Signal-Regulated MAP Kinases; D019703:Calcineurin; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C489931:Ptpn5 protein, rat