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Assessment of cognitive function in the heterozygous reeler mouse

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Abstract

Rationale

The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined.

Objective

Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.

Methods

Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task, (2) impulsivity in an inhibitory control task, (3) attentional function in a three-choice serial reaction time task, and (4) working memory in a delayed matching-to-position task.

Results

No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning.

Conclusions

These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.

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Acknowledgments

This work was supported by NIH grants MH 74866, MH 40899, and DA11717, as well as the Scottish Rite Schizophrenia Research Program.

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Correspondence to Angus C. Nairn.

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Krueger, D.D., Howell, J.L., Hebert, B.F. et al. Assessment of cognitive function in the heterozygous reeler mouse. Psychopharmacology 189, 95–104 (2006). https://doi.org/10.1007/s00213-006-0530-0

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  • DOI: https://doi.org/10.1007/s00213-006-0530-0

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