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

Full 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.

Author information

Author/s: Rutten, K (K); Basile, J L (JL); Prickaerts, J (J); Blokland, A (A); Vivian, J A (JA);

Affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, PO Box 616, 6200 MD Maastricht, The Netherlands. k.rutten(-atsign-)np.unimaas.nl

Journal and publication information

Publication Type: Journal Article

Journal: Psychopharmacology (Psychopharmacology (Berl)), published in Germany. (Language: eng)

Reference: 2008-Mar; vol 196 (issue 4) : pp 643-8

Dates: Created 2008/02/15; Completed 2008/08/14; Revised 2008/11/20;

PMID: 18034336, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Attention - drug effects; physiology
Cognition - drug effects; physiology
Injections, Intramuscular
Macaca fascicularis
Male
Mental Recall - drug effects; physiology
Phosphodiesterase Inhibitors - pharmacology

Phosphodiesterase Inhibitors - pharmacology
Piperazines - pharmacology
Prefrontal Cortex - drug effects; physiology
Problem Solving - drug effects; physiology
Psychomotor Performance - drug effects; physiology
Purines - pharmacology
Rolipram - pharmacology
Sulfones - pharmacology

Associated Chemicals: Phosphodiesterase Inhibitors (0) ; Piperazines (0) ; Purines (0) ; Sulfones (0) ; sildenafil (139755-83-2) ; Rolipram (61413-54-5)

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