title: Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801.
abstract: The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1mg/kg (p.o.) in the scopolamine model and 0.3-3mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1mg/kg) and PQ-10 (0.3mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement.
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
authors.forename: Olga A H
authors.initials: OAH
authors.lastname: Reneerkens
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
authors.forename: Kris
authors.initials: K
authors.lastname: Rutten
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Bollen
authors.affiliation: biocrea, Radebeul, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hage
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
authors.forename: Harry W M
authors.initials: HWM
authors.lastname: Steinbusch
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors*; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D005106:Exploratory Behavior / Q000187:drug effects; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D018727:Muscarinic Antagonists; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012601:Scopolamine; D021241:Spectrometry, Mass, Electrospray Ionization; D014227:Triazines / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C539142:2-(3,4-dimethoxybenzyl)-7-(1-(1-hydroxyethyl)-4-phenylbutyl)-5-methylimidazo(5,1-f)(1,2,4)triazin-4 (3H)-one; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D018727:Muscarinic Antagonists; D010726:Phosphodiesterase Inhibitors; D014227:Triazines; D016291:Dizocilpine Maleate; D012601:Scopolamine; C512064:PDE10A protein, rat; D010727:Phosphoric Diester Hydrolases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2