Atorvastatin improved scopolamine-induced impairment in memory acquisition in mice: involvement of nitric oxide

Brain Res. 2011 Apr 22:1386:89-99. doi: 10.1016/j.brainres.2011.02.057. Epub 2011 Feb 23.

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.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Atorvastatin
  • Cholinergic Antagonists / pharmacology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Guanidines / pharmacology
  • Heptanoic Acids / pharmacology*
  • Heptanoic Acids / therapeutic use
  • Learning Disabilities / chemically induced
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / physiopathology
  • Memory / drug effects
  • Memory / physiology
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Scopolamine / pharmacology

Substances

  • Cholinergic Antagonists
  • Enzyme Inhibitors
  • Guanidines
  • Heptanoic Acids
  • Pyrroles
  • Nitric Oxide
  • Arginine
  • Atorvastatin
  • Scopolamine
  • Nitric Oxide Synthase
  • pimagedine
  • NG-Nitroarginine Methyl Ester