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

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.