title: Morphine preconditioning protects against LPS-induced neuroinflammation and memory deficit.
abstract: Recent studies show that morphine possesses protective preconditioning effects in different ischemia/reperfusion models. However, there is very little information about the antineuroinflammatory role of morphine and its protective effect against memory deficit. In the present study, we evaluated the role of morphine preconditioning in a model of mild neuroinflammation induced by intraperitoneal lipopolysaccharide (LPS) injection (1 mg/kg). Rats were trained on passive avoidance apparatus and challenged with LPS 20 h later. Four hours after LPS, rats were subjected to passive avoidance testing and then for the assessments of inflammatory and apoptotic cell death mediators in the hippocampus. LPS significantly increased the nuclear NF-κB and expression of COX-2, IL-1β, and TNF-α, augmented the activity of caspase-3 and PARP cleavage, and in parallel shortened the latencies to enter the dark compartment. Although morphine injection in a noninflammatory context was able to induce a neuroinflammatory response and memory loss, morphine preconditioning at the dose of 4 mg/kg significantly prevented the LPS-induced neuroinflammation and memory deficit. Morphine preconditioning was abolished by naloxone and, therefore, is dependent on opioid receptors. These results suggest that acute morphine injection, in spite of the induction of a neuroinflammatory response and amnesia per se, exerts an antineuroinflammatory role and protects from cell death and memory deficit in an inflammatory context.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Rostami
authors.forename: Shahrbanoo
authors.initials: S
authors.lastname: Oryan
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.forename: Leila
authors.initials: L
authors.lastname: Dargahi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002545:Brain Ischemia / Q000139:chemically induced / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy*; D019194:Ischemic Preconditioning / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505410:Casp3 protein, rat; D053148:Caspase 3