Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice

Brain Res. 2012 Jan 6;1429:61-71. doi: 10.1016/j.brainres.2011.08.006. Epub 2011 Aug 9.

Abstract

Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience.

MeSH terms

  • Animals
  • Cholinergic Antagonists / toxicity
  • Enzyme Inhibitors / pharmacology
  • Granisetron / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory / physiology*
  • Memory Disorders / chemically induced
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Scopolamine / toxicity
  • Serotonin Antagonists / pharmacology*

Substances

  • Cholinergic Antagonists
  • Enzyme Inhibitors
  • Serotonin Antagonists
  • Nitric Oxide
  • Scopolamine
  • NG-Nitroarginine Methyl Ester
  • Granisetron