Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801

Behav Brain Res. 2013 Jan 1;236(1):16-22. doi: 10.1016/j.bbr.2012.08.019. Epub 2012 Aug 19.


The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1mg/kg (p.o.) in the scopolamine model and 0.3-3mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1mg/kg) and PQ-10 (0.3mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / antagonists & inhibitors*
  • Dizocilpine Maleate*
  • Excitatory Amino Acid Antagonists*
  • Exploratory Behavior / drug effects
  • Imidazoles / pharmacokinetics
  • Imidazoles / pharmacology
  • Male
  • Memory / drug effects
  • Memory Disorders / chemically induced*
  • Memory Disorders / drug therapy*
  • Memory Disorders / psychology
  • Muscarinic Antagonists*
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / metabolism*
  • Rats
  • Rats, Wistar
  • Recognition, Psychology / drug effects
  • Scopolamine*
  • Spectrometry, Mass, Electrospray Ionization
  • Triazines / pharmacokinetics
  • Triazines / pharmacology


  • 2-(3,4-dimethoxybenzyl)-7-(1-(1-hydroxyethyl)-4-phenylbutyl)-5-methylimidazo(5,1-f)(1,2,4)triazin-4 (3H)-one
  • Excitatory Amino Acid Antagonists
  • Imidazoles
  • Muscarinic Antagonists
  • Phosphodiesterase Inhibitors
  • Triazines
  • Dizocilpine Maleate
  • Scopolamine
  • PDE10A protein, rat
  • Phosphoric Diester Hydrolases
  • Cyclic Nucleotide Phosphodiesterases, Type 2