Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: effects of 7-nitroindazole and zaprinast

Eur J Pharmacol. 1997 Oct 22;337(2-3):125-36. doi: 10.1016/s0014-2999(97)01301-0.

Abstract

The effects of 7-nitroindazole, a putative selective inhibitor of neuronal nitric oxide (NO) synthase and zaprinast, a cGMP-selective phosphodiesterase inhibitor, were evaluated on recognition memory of rats in the object recognition test. This test is based on the differential exploration of a new and a familiar object. Two doses of 7-nitroindazole (10 and 30 mg/kg) and zaprinast (3 and 10 mg/kg) were used. The substances were administered i.p. immediately after the exposure to two identical objects, i.e., at the start of the delay interval. After a delay interval of 1 h, control rats spent more time exploring the new object which demonstrates that they recognized the familiar one. Both doses of 7-nitroindazole impaired the discrimination between the two objects after the 1 h interval. After a 4 h interval, control rats did not discriminate between the objects. The highest dose of zaprinast facilitated object recognition after the 4 h interval. In addition, this dose of zaprinast (10 mg/kg) reversed the recognition memory deficit induced by 7-nitroindazole (10 mg/kg) at the 1 h interval. The highest dose of 7-nitroindazole slightly increased mean arterial blood pressure 1 h after its administration. 4 h after administration of zaprinast (10 mg/kg), mean arterial blood pressure was also slightly increased, but not after 1 h after zaprinast administration. However, these effects on blood pressure do not explain the differential effects on object recognition memory. These results therefore suggest that NO-cGMP signal transduction is involved in object recognition memory independently of its cardiovascular role. Finally, since 7-nitroindazole affected mean arterial blood pressure it can not be regarded as a selective inhibitor of neuronal NO synthase.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cyclic GMP / physiology*
  • Drug Interactions
  • Exploratory Behavior / drug effects
  • Indazoles / pharmacology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Phosphodiesterase Inhibitors / pharmacology
  • Purinones / pharmacology*
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Visual Perception / drug effects
  • Visual Perception / physiology*

Substances

  • Indazoles
  • Phosphodiesterase Inhibitors
  • Purinones
  • Nitric Oxide
  • Nitric Oxide Synthase
  • zaprinast
  • Cyclic GMP
  • 7-nitroindazole