Donepezil and the alpha-7 agonist PHA 568487, but not risperidone, ameliorate spatial memory deficits in a subchronic MK-801 mouse modet of cognitive impairment in schizophrenia

Stoyo Karamihalev, Jos Prickaerts*, Nick P. van Goethem

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)248-251
JournalBehavioural Brain Research
Publication statusPublished - 1 Oct 2014


  • Alpha-7 agonist
  • Donepezil
  • Memory
  • Risperidone
  • Schizophrenia
  • Subchronic MK-801

Cite this