Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors

Eur J Pharmacol. 2007 Mar 8;558(1-3):107-12. doi: 10.1016/j.ejphar.2006.11.041. Epub 2006 Dec 1.

Abstract

The present study investigated the time-dependent memory enhancing properties of three selective phosphodiesterase inhibitors (PDE-I) vardenafil (PDE5-I), rolipram (PDE4-I) and BAY 60-7550 (PDE2-I) in the object recognition task. In particular, the time-dependent involvement of cAMP and cGMP in memory consolidation was assessed by altering the time points of drug administration. Vardenafil (1 mg/kg, p.o.), rolipram (0.03 mg/kg, i.p.), and BAY 60-7550 (3 mg/kg, p.o.) were tested in rats with a 24 h delay between the learning and the test trial. The PDE-Is were administered at different time points, i.e. directly after, 1 h, 3 h and 6 h after the first trial. Using a 24 h interval, vardenafil only showed an effect on object memory when injected directly after trial 1, rolipram only showed an improvement when injected 3 h after trial 1 and BAY 60-7550 improved memory when injected either directly after or 3 h after trial 1. No treatment effects were found when the compounds were administered 1 h or 6 h after the first trial. Our results extend our previous data that different types of PDE-Is affect different stages of memory consolidation. Moreover, the present study provides further support that selective PDE-Is can influence memory consolidation in a time-dependent manner, assumingly by elevating central cAMP and cGMP levels.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Cyclic AMP / physiology*
  • Cyclic GMP / physiology*
  • Cyclic Nucleotide Phosphodiesterases, Type 2
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Imidazoles / pharmacology
  • Male
  • Memory / drug effects*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / drug effects*
  • Piperazines / pharmacology
  • Rats
  • Rats, Wistar
  • Rolipram / pharmacology
  • Sulfones / pharmacology
  • Time Factors
  • Triazines / pharmacology
  • Vardenafil Dihydrochloride

Substances

  • Imidazoles
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 2
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Pde2a protein, rat
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Pde5a protein, rat
  • Cyclic GMP
  • Rolipram