title: Possible interaction of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II on reversal of spatial memory impairment induced by morphine.
abstract: The opioid system plays an important role in learning and memory by modulation of different molecules in the brain. The aim of the present study was to investigate the role of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II (CaMKII) on the morphine-induced modulation of spatial memory consolidation in male rats. Spatial memory was assessed in Morris water maze task by a single training session of eight trials followed by a probe trial and visible test 24h later. Our data indicated that post-training administration of L-arginine, a nitric oxide precursor (6 and 9 µg/rat, intra-CA1) significantly decreased amnesia induced by morphine (10 mg/kg) in spatial memory consolidation. A reversal effect of L-arginine on morphine-induced amnesia prevented by KN-93 (N-[2-(N-(4-chlorocinnamyl)-N-methylaminomethyl) phenyl]-N-[2-hydroxyethyl] methoxybenzenesulfnamide), CaMKII inhibitor, (10 nmol/0.5 µl/site). In addition, post-training injection of L-NAME, (NG-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (10 and 15 µg/rat) or KN-93 (10 nmol/0.5 µl/site) with lower dose of morphine (2.5 mg/kg), which did not induce amnesia by itself, caused inhibition of memory consolidation. We also showed that co-administration of L-arginine (9 µg/rat) and morphine (10 mg/kg) significantly increased CaMKII activity in the rat hippocampus. On the other hand, administration of L-NAME (10 µg/rat) led to a decrease in the haippocampal activity of CaMKII in morphine-treated (2.5mg/kg) animals. These results indicate that acute single exposure to morphine can modulate consolidation of spatial memory, which may be mediated by a hippocampal nitrergic system and CaMKII activity.
authors: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mfarahmandfar@razi.tums.ac.ir.
authors: Maryam
authors: M
authors: Farahmandfar
authors: Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
authors: Mehdi
authors: M
authors: Kadivar
authors: Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
authors: Nasser
authors: N
authors: Naghdi
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects; D009020:Morphine / Q000009:adverse effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019331:NG-Nitroarginine Methyl Ester
keywords: CA1; CaMKII; Morphine; Nitric oxide; Rat; Spatial memory