title: Chronic administration of atypical antipsychotics improves behavioral and synaptic defects of STOP null mice.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: SynapCell SAS, Bâtiment Biopolis, 5 avenue du Grand Sablon, 38700, La Tronche, France.
authors: David
authors: D
authors: Delotterie
authors: Geoffrey
authors: G
authors: Ruiz
authors: Jacques
authors: J
authors: Brocard
authors: Annie
authors: A
authors: Schweitzer
authors: Corinne
authors: C
authors: Roucard
authors: Yann
authors: Y
authors: Roche
authors: Marie-Françoise
authors: MF
authors: Suaud-Chagny
authors: Karine
authors: K
authors: Bressand
authors: Annie
authors: A
authors: Andrieux
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D003024:Clozapine; D018967:Risperidone