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Chronic administration of atypical antipsychotics improves behavioral and synaptic defects of STOP null mice.

Abstract : INTRODUCTION: Recent studies have suggested that schizophrenia is associated with alterations in the synaptic connectivity involving cytoskeletal proteins. The microtubule-associated protein stable tubule only polypeptide (STOP) plays a key role in neuronal architecture and synaptic plasticity, and it has been demonstrated that STOP gene deletion in mice leads to a phenotype mimicking aspects of positive and negative symptoms and cognitive deficits classically observed in schizophrenic patients. In STOP null mice, behavioral defects are associated with synaptic plasticity abnormalities including defects in long-term potentiation. In these mice, long-term administration of typical antipsychotics has been shown to partially alleviate behavioral defects but, as in humans, such a treatment was poorly active on deficits related to negative symptoms and cognitive impairments. Here, we assessed the effects of risperidone and clozapine, two atypical antipsychotics, on STOP null mice behavior and synaptic plasticity. RESULTS: Long-term administration of either drug results in alleviation of behavioral alterations mimicking some negative symptoms and partial amelioration of some cognitive defects in STOP null mice. Interestingly, clozapine treatment also improves synaptic plasticity of the STOP null animals by restoring long-term potentiation in the hippocampus. DISCUSSION: All together, the pharmacological reactivity of STOP null mice to antipsychotics evokes the pharmacological response of humans to such drugs. Totally, our study suggests that STOP null mice may provide a useful preclinical model to evaluate pharmacological properties of antipsychotic drugs.
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Submitted on : Friday, January 15, 2010 - 5:58:32 PM
Last modification on : Thursday, May 28, 2020 - 10:42:02 AM
Long-term archiving on: : Thursday, June 17, 2010 - 9:19:36 PM

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David Delotterie, Geoffrey Ruiz, Jacques Brocard, Annie Schweitzer, Corinne Roucard, et al.. Chronic administration of atypical antipsychotics improves behavioral and synaptic defects of STOP null mice.. Psychopharmacology, Springer Verlag, 2010, 208 (1), pp.131-41. ⟨10.1007/s00213-009-1712-3⟩. ⟨inserm-00447474⟩

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