title: PDE and cognitive processing: beyond the memory domain.
abstract: Phosphodiesterase inhibitors (PDE-Is) enhance cAMP and/or cGMP signaling via reducing the degradation of these cyclic nucleotides. Both cAMP and cGMP signaling are essential for a variety of cellular functions and exert their effects both pre- and post-synaptically. Either of these second messengers relays and amplifies incoming signals at receptors on the cell surface making them important elements in signal transduction cascades and essential in cellular signaling in a variety of cell functions including neurotransmitter release and neuroprotection. Consequently, these processes can be influenced by PDE-Is as they increase cAMP and/or cGMP concentrations. PDE-Is have been considered as possible therapeutic agents to treat impaired memory function linked to several brain disorders, including depression, schizophrenia and Alzheimer's disease (AD). This review will, however, focus on the possible role of phosphodiesterases (PDEs) in cognitive decline beyond the memory domain. Here we will discuss the involvement of PDEs on three related domains: attention, information filtering (sensory- and sensorimotor gating) and response inhibition (drug-induced hyperlocomotion). Currently, these are emerging cognitive domains in the field of PDE research. Here we discuss experimental studies and the potential beneficial effects of PDE-I drugs on these cognitive domains, as effects of PDE-Is on these domains could potentially influence effects on memory performance. Overall, PDE4 seems to be the most promising target for all domains discussed in this review.
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands; Department of Neuropsychology and Psychopharmacology, Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: P R A
authors.initials: PR
authors.lastname: Heckman
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Blokland
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Ramaekers
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
authors.forename: J
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects / Q000502:physiology; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: Attention; Gating; PDE; Response inhibition; cAMP; cGMP