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 ~50 to ~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.
Keywords Attention - Executive function - Phosphodiesterase - PDE4 - Rolipram - PDE5 - Sildenafil - Cognition - Cyclic AMP - Cyclic GMP - Object retrieval - Monkey - Primate