ro-25-6981 and morpholine

Stress impairs hippocampal long-term potentiation (LTP), but it is unknown whether the stress evoked by opiate withdrawal has the same effect. Here the authors report that opiate withdrawal for 4 days does not influence basal synaptic transmission, but results in a greatly increased LTP in hippocampal CA1 area in anesthetized rats. Elevated-platform stress enabled a large LTP in rats withdrawn for only 18 h, but the glucocorticoid receptor antagonist RU38486 (twice per day for 3 days) prevented the large LTP on 4 days withdrawal. Moreover, 4 days withdrawal enhanced the NMDAR-mediated EPSCs, in which the NR2A-containing NMDAR-mediated EPSC was increased but the NR2B-containing NMDAR-mediated EPSC was decreased. These results suggest that adaptive changes of the NMDAR and glucocorticoid receptor functions during 4 days of opiate withdrawal may enable stress to facilitate hippocampal LTP, potentially contributing to the opiate withdrawal experience-dependent modifications of hippocampal functions.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Analysis of Variance; Animals; Dose-Response Relationship, Radiation; Drug Administration Schedule; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hippocampus; Hormone Antagonists; In Vitro Techniques; Long-Term Potentiation; Male; Mifepristone; Morpholines; Patch-Clamp Techniques; Phenols; Piperidines; Rats; Rats, Sprague-Dawley; Stress, Psychological; Substance Withdrawal Syndrome; Time Factors