title: The role of nitric oxide in the PKA inhibitor induced spatial memory deficits in rat: involvement of choline acetyltransferase.
abstract: Several lines of evidence show that cAMP-PKA signaling pathway plays critical role in memory functions and suggest nitric oxide as an important modulator in learning and memory. In this study, we assessed the effects of intra-hippocampal infusion of H-89, a selective PKAII inhibitor, and 1400 W, a selective inducible nitric oxide synthase (iNOS) inhibitor, on spatial memory in rats. By using the Morris water maze, spatial memory retention parameters were examined 48 h after the infusions through measuring escape latency, traveled distance, and swimming speed. The rats receiving intra-hippocampal infusions of 1400 W (100 µM/side) showed a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the control saline group. In contrast, a significant increase (**P<0.01) in escape latency and traveled distance was observed after infusion of 10 µM H-89. Moreover, among combination groups, co-administration of 1400 W (400 µM/side) with 10 µM/side of H-89 caused a significant reduction (*P<0.05) in escape latency and traveled distance in comparison with the H-89 group. Also, we evaluated the molecular effects of 1400 W on the expression of choline acetyltransferase (ChAT), a cholinergic marker, in the CA1 region of the hippocampus and medial septal area (MSA). Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400 W revealed a significant increase in ChAT immunoreactivity levels in both the CA1 and the MSA regions. Overall, the results suggest that 1400 W has protective effect against H89-induced spatial memory impairment. Moreover, the observed memory improvements caused by 1400 W infusions, might be due to interaction of iNOS with the cholinergic system.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sheyda
authors.initials: S
authors.lastname: Najafi
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Kaveh
authors.initials: K
authors.lastname: Tabrizian
authors.forename: Marjan
authors.initials: M
authors.lastname: Shariatpanahi
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nassireslami
authors.forename: Kian
authors.initials: K
authors.lastname: Azami
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Farideh
authors.initials: F
authors.lastname: Asadi
authors.forename: Ali
authors.initials: A
authors.lastname: Roghani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007097:Imines / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013550:Swimming
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D007097:Imines; D007546:Isoquinolines; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D009569:Nitric Oxide; D002795:Choline O-Acetyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Inducible nitric oxide synthase; Morris water maze; Protein kinase A; Spatial memory