Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques

Psychopharmacology (Berl). 2008 Mar;196(4):643-8. doi: 10.1007/s00213-007-0999-1. Epub 2007 Nov 23.

Abstract

Rationale: Selective phosphodiesterase (PDE) inhibitors improve the formation of hippocampus-dependent memories in several rodent models of cognition. However, studies evaluating the effects of PDE inhibition on prefrontal cortex-dependent cognition and in monkeys are rare.

Objectives: The present study investigates the effect of the PDE4 inhibitor rolipram and the PDE5 inhibitor sildenafil on object retrieval performance. Object retrieval is a prefrontal cortical-mediated task, which is likely to capture attention and response inhibition.

Materials and methods: The ability to retrieve a food reward from a clear box with an open side positioned in various orientations was assessed in adult male cynomolgus monkeys (Macaca fascicularis).

Results: Rolipram (0.003-0.03 mg/kg, intramuscular [i.m.]) and sildenafil (0.3-3 mg/kg, i.m.) dose-dependently increased correct first reaches during difficult trials, reaching significance at 0.01 and 1 mg/kg, respectively. For both drugs, correct reaches were increased approximately 20%; that is, performance was improved from approximately 50 to approximately 70% correct.

Conclusions: Both rolipram and sildenafil improved object retrieval performance, thus demonstrating the cognition-enhancing effects of PDE inhibition on a prefrontal task of executive function in monkeys.

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology
  • Cognition / drug effects
  • Cognition / physiology
  • Injections, Intramuscular
  • Macaca fascicularis
  • Male
  • Mental Recall / drug effects*
  • Mental Recall / physiology
  • Phosphodiesterase Inhibitors / pharmacology*
  • Piperazines / pharmacology*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology
  • Problem Solving / drug effects
  • Problem Solving / physiology
  • Psychomotor Performance / drug effects*
  • Psychomotor Performance / physiology
  • Purines / pharmacology
  • Rolipram / pharmacology*
  • Sildenafil Citrate
  • Sulfones / pharmacology*

Substances

  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate
  • Rolipram