PDE2 and PDE10, but not PDE5, inhibition affect basic auditory information processing in rats

Behav Brain Res. 2013 Aug 1;250:251-6. doi: 10.1016/j.bbr.2013.05.014. Epub 2013 May 17.

Abstract

Phosphodiesterase type 2 (PDE2), type 10 (PDE10), and type 5 (PDE5) have been considered as relevant targets for cognition enhancement. Although it is well established that PDE inhibitors (PDE-Is) improve memory functions in animals, the effects on auditory information processing are less clear. The aim of this study was to test the effects of PDE2 (BAY 60-7550), PDE5 (vardenafil) and PDE10 (PQ-10) inhibition on sensory gating in rats. Vehicle or 1mg/kg of a specific PDE-I was given orally 30min before testing. EEG was recorded from the hippocampus, striatum and vertex. Sensory gating was found for the N1 in the vertex and hippocampus, as revealed by diminished amplitudes to S2 compared to S1. Administration of PDE-Is did not affect sensory gating. However, PDE2 inhibition increased the P1 peak after presentation of S1 at the vertex and PQ-10 increased the N1 peak in general compared to vehicle treatment at the hippocampus. PDE2 and PDE10 inhibition affect auditory information processing in general, whereas PDE5 inhibition has no effect. These findings suggest that the positive effects of PDE5 inhibition on cognition previously found in animals are possibly the results of an effect on higher cognitive functioning specifically, whereas the cognition enhancing effects of PDE2 and PDE10 inhibition might also be influenced by effects on earlier stages of information processing.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Brain / drug effects
  • Brain / physiology
  • Brain Waves / drug effects
  • Brain Waves / physiology*
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / antagonists & inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Drug Interactions
  • Male
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / metabolism*
  • Psychoacoustics
  • Rats
  • Rats, Wistar
  • Sensory Gating / drug effects
  • Sensory Gating / physiology*

Substances

  • Phosphodiesterase Inhibitors
  • PDE10A protein, rat
  • Phosphoric Diester Hydrolases
  • Cyclic Nucleotide Phosphodiesterases, Type 2
  • Cyclic Nucleotide Phosphodiesterases, Type 5