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Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task

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Abstract

Rationale

Atypical antipsychotics improve cognitive function, including working memory, in schizophrenia. Some atypical antipsychotics have been reported to activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c-Fos-like immunoreactivity in the prefrontal cortex.

Materials and methods

The present study investigated the effects of chronic treatment of rats with risperidone (1 mg kg−1 day−1 s.c.), clozapine (10 mg kg−1 day−1 s.c.), or acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory performance in a delayed matching-to-place water maze task with a 60-s inter-trial retention interval with and without acute challenge with propranolol (10 mg/kg i.p.).

Results

Treatment with risperidone for 8 weeks, but not 2 or 4 weeks, significantly improved working memory performance. In contrast, treatment with clozapine for up to 8 weeks did not improve working memory. Acute challenge with propranolol blocked the improvement in working memory produced by chronic treatment with risperidone, but had no significant effect on performance in saline- or clozapine-treated animals.

Conclusions

The delayed matching-to-place water maze task may prove valuable in the investigation of the behavioural pharmacology of the cognitive effects of antipsychotic drugs. These data suggest that beta adrenoceptors may contribute to the cognitive effects of chronic treatment with atypical antipsychotics.

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Acknowledgement

This study was supported by a grant from the Academic Research Fund of the National University of Singapore to Dr Gavin S. Dawe (R-184-000-045-112).

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  1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Building MD2, 18 Medical Drive, Singapore, 117597, Singapore

    Ee Peng Lim, Vivek Verma, Rajini Nagarajah & Gavin S. Dawe

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  1. Ee Peng Lim
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Correspondence to Gavin S. Dawe.

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Lim, E.P., Verma, V., Nagarajah, R. et al. Propranolol blocks chronic risperidone treatment-induced enhancement of spatial working memory performance of rats in a delayed matching-to-place water maze task. Psychopharmacology 191, 297–310 (2007). https://doi.org/10.1007/s00213-006-0664-0

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