期刊
BEHAVIOURAL BRAIN RESEARCH
卷 272, 期 -, 页码 248-251出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2014.07.017
关键词
Alpha-7 agonist; Donepezil; Memory; Risperidone; Schizophrenia; Subchronic MK-801
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 (0.1 mg/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. (C) 2014 Elsevier B.V. All rights reserved.
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