title: Donepezil and the alpha-7 agonist PHA 568487, but not risperidone, ameliorate spatial memory deficits in a subchronic MK-801 mouse model of cognitive impairment in schizophrenia.
abstract: Cognitive impairment associated with schizophrenia (CIAS) is an important etiological feature of this disorder with implications for symptom severity and quality of life. Acute N-methyl-d-aspartate receptor (NMDAR) blockade using MK-801, a non-competitive antagonist to NMDARs, is assumed to produce temporary cognitive impairments in mice similar to those seen in schizophrenia patients. Less is known, however, about the effects of subchronic MK-801 administration on cognition. In the current study, twenty-eight male C57/BL6 mice received a daily dose of MK-801 (0.1mg/kg, i.p.) for seven days. Spatial memory was assessed using an object location task prior to MK-801 administration as well as at multiple time points after the treatment. Subchronic treatment with MK-801 caused lasting memory deficits, which were ameliorated by acute doses of an acetylcholinesterase inhibitor (donepezil) and an alpha-7 nicotinic agonist (PHA 568487), but were unaffected by acute administration of the atypical antipsychotic risperidone. Subchronic administration of MK-801 may lend this pharmaceutical model increased face validity, while its resemblance to prodromal schizophrenia makes it suitable for screening new CIAS treatments.
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors.forename: Stoyo
authors.initials: S
authors.lastname: Karamihalev
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands. Electronic address: jos.prickaerts@maastrichtuniversity.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, The Netherlands.
authors.forename: Nick P
authors.initials: NP
authors.lastname: van Goethem
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001372:Aza Compounds / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004147:Dioxins / Q000494:pharmacology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D018967:Risperidone / Q000494:pharmacology*; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D065852:Spatial Memory / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D001372:Aza Compounds; D002800:Cholinesterase Inhibitors; D004147:Dioxins; D007189:Indans; D018722:Nicotinic Agonists; D018697:Nootropic Agents; C514026:PHA-568487E; D010880:Piperidines; D064569:alpha7 Nicotinic Acetylcholine Receptor; D016291:Dizocilpine Maleate; D000077265:Donepezil; D000110:Acetylcholinesterase; D018967:Risperidone
keywords: Alpha-7 agonist; Donepezil; Memory; Risperidone; Schizophrenia; Subchronic MK-801