Phosphodiesterase type 5 inhibition improves early memory consolidation of object information

• Published in: Neurochemistry international 2004-11, Vol.45 (6), p.915-928
• Main Authors: Prickaerts, Jos, Şık, Ayhan, van Staveren, Wilma C.G, Koopmans, Guido, Steinbusch, Harry W.M, van der Staay, Franz Josef, Vente, Jan de, Blokland, Arjan
• Format: Article
• Language: English
• Subjects: 14-unit t-maze; 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Avoidance Learning - drug effects; Biological and medical sciences; Brain Chemistry - physiology; c-fos expression; cerebral-blood-flow; cGMP; Cognition - drug effects; Consolidation; cultured hippocampal-neurons; Cyclic GMP - physiology; Cyclic Nucleotide Phosphodiesterases, Type 5; cyclic-gmp; dependent protein-kinase; Fundamental and applied biological sciences. Psychology; Humans; late-phase ltp; Learning - drug effects; long-term potentiation; Long-Term Potentiation - drug effects; Memory; Memory - drug effects; nitric-oxide synthase; Object; PDE5; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - metabolism; soluble guanylyl cyclase; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2004.03.022

The nitric oxide (NO)-cyclic GMP (cGMP) signaling pathway is assumed to play an important role in processes underlying learning and memory. We used phosphodiesterase type 5 (PDE5) inhibitors to study the role of cGMP in object- and spatial memory. Our results and those reported in other studies indicate that elevated hippocampal cGMP levels are required to improve the memory performance of rodents in object recognition and passive avoidance learning, but not in spatial learning. The timing of treatment modulates the effects on memory and strongly supports a role for cGMP in early stages of memory formation. Alternative explanations for the improved memory performance of PDE5 inhibitors are also discussed. Immunocytochemical studies showed that in vitro slice incubations with PDE5 inhibitors increase NO-stimulated cGMP levels mainly in hippocampal varicose fibers. Reviewing the available data on the localization of the different components of the NO-cGMP signaling pathway, indicates a complex interaction between NO and cGMP, which may be independent of each other. It is discussed that further studies are needed, immunocytochemical and behavioral, to better understand the cGMP-mediated molecular mechanisms underlying memory formation.