Elsevier

Behavioural Brain Research

Volume 272, 1 October 2014, Pages 248-251
Behavioural Brain Research

Short Communication
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

https://doi.org/10.1016/j.bbr.2014.07.017Get rights and content

Highlights

  • Subchronic administration of MK-801 produces long-term memory deficits in mice.

  • Memory is restored by an acetylcholinesterase inhibitor or an alpha-7 agonist.

  • The atypical antipsychotic risperidone does not ameliorate memory deficits.

  • The subchronic MK-801 model has improved face validity for CIAS.

  • The current model may be of use for screening new treatments for CIAS.

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 (0.1 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.

Section snippets

Conflict of interest

The authors declare no conflicts of interest.

Acknowledgement

The authors would like to thank Thecla van Wageningen for her technical assistance.

References (25)

  • D.C. Javitt

    Twenty-five years of glutamate in schizophrenia: are we there yet?

    Schizophr Bull

    (2012)
  • H.Y. Meltzer et al.

    Translating the N-methyl-d-aspartate receptor antagonist model of schizophrenia to treatments for cognitive impairment in schizophrenia

    Int J Neuropsychopharmacol

    (2013)
  • Cited by (0)

    1

    Both authors contributed equally to this work.

    View full text