title: Repetitive systemic morphine alters activity-dependent plasticity of Schaffer-collateral-CA1 pyramidal cell synapses: involvement of adenosine A1 receptors and adenosine deaminase.
abstract: The effectiveness of O-pulse stimulation (TPS) for the reversal of O-pattern primed bursts (PB)-induced long-term potentiation (LTP) were examined at the Schaffer-collateral-CA1 pyramidal cell synapses of hippocampal slices derived from rats chronically treated with morphine (M-T). The results showed that slices derived from both control and M-T rats had normal field excitatory postsynaptic potential (fEPSP)-LTP, whereas PS-LTP in slices from M-T rats was significantly greater than that from control slices. When morphine was applied in vitro to slices derived from rats chronically treated with morphine, the augmentation of PS-LTP was not seen. TPS given 30 min after LTP induction failed to reverse the fEPSP- or PS-LTP in both groups of slices. However, TPS delivered in the presence of long-term in vitro morphine caused the PS-LTP reversal. This effect was blocked by the adenosine A1 receptor (A1R) antagonist CPX (200 nM) and furthermore was enhanced by the adenosine deaminase (ADA) inhibitor EHNA (10 μM). Interestingly, TPS given 30 min after LTP induction in the presence of EHNA (10 μM) can reverse LTP in morphine-exposed control slices in vitro. These results suggest adaptive changes in the hippocampus area CA1 in particular in adenosine system following repetitive systemic morphine. Chronic in vivo morphine increases A1R and reduces ADA activity in the hippocampus. Consequently, adenosine can accumulate because of a stimulus train-induced activity pattern in CA1 area and takes the opportunity to work as an inhibitory neuromodulator and also to enable CA1 to cope with chronic morphine. In addition, adaptive mechanisms are differentially working in the dendrite layer rather than the somatic layer of hippocampal CA1.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sadegh
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Fathollahi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D004791:Enzyme Inhibitors; D009294:Narcotics; D043682:Receptor, Adenosine A1; D014970:Xanthines; C010192:9-(2-hydroxy-3-nonyl)adenine; D009020:Morphine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000243:Adenosine Deaminase; D000225:Adenine
keywords: P burst; adenosine A1 receptor; adenosine deaminase; fEPSP; sodium-salicylate; synaptic modulation; theta pulse