title: Atorvastatin improved scopolamine-induced impairment in memory acquisition in mice: involvement of nitric oxide.
abstract: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, widely used in treatment of hypercholesterolemia, slows the progression of mild-to-moderate Alzheimer's disease. In this study, effects of atorvastatin on acquisition of spatial recognition memory and the involvement of nitric oxide (NO) have been determined in a two-trial recognition Y-maze test and passive avoidance. Atorvastatin (1, 5mg/kg, p.o.) was administered prior to acquisition phase, either in presence or in absence of a non-specific NO synthase inhibitor, L-NAME (3, 10mg/kg, i.p.); a specific inducible NO synthase inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750mg/kg).
  
  
  RESULTS
  Atorvastatin significantly improved memory performance in a dose-dependent manner in acquisition of recognition memory, in both Y-maze and passive avoidance tests. 1) Atorvastatin (5mg/kg) significantly increased both exploration time and number of arm entries in scopolamine-treated mice in Y-maze. 2) The beneficial effects of atorvastatin on memory acquisition were significantly reversed by L-NAME (3mg/kg) and aminoguanidine (100mg/kg). 3) The effects of sub-effective dose of atorvastatin (1mg/kg) on memory acquisition were not potentiated by l-arginine (750mg/kg); 4) Administration of atorvastatin (5mg/kg) significantly increased step-through latency in scopolamine-induced memory-impaired mice. 5) Beneficial effect of atorvastatin on passive avoidance was not reversed by L-NAME (up to 10mg/kg). 6) The effects of sub-effective dose of atorvastatin (1mg/kg) on passive avoidance were not potentiated by l-arginine (750mg/kg). The present study demonstrates that atorvastatin improved both short-spatial recognition memory and fear memory. As this effect is reversed by L-NAME and aminoguanidine in short-term memory acquisition, it is concluded that NO might be involved in spatial memory improvement by atorvastatin.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehrak
authors.initials: M
authors.lastname: Javadi-Paydar
authors.forename: Farhoud
authors.initials: F
authors.lastname: Rayatnia
authors.forename: Nahid
authors.initials: N
authors.lastname: Fakhraei
authors.forename: Marjan
authors.initials: M
authors.lastname: Zakeri
authors.forename: Naser
authors.initials: N
authors.lastname: Mirazi
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D000069059:Atorvastatin; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D006146:Guanidines; D006538:Heptanoic Acids; D011758:Pyrroles; D009569:Nitric Oxide; D001120:Arginine; D000069059:Atorvastatin; D012601:Scopolamine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester