Potential application as screening and drug designing tools of cytoarchitectural deficiencies present in three animal models of schizophrenia

Alfredo Bellon, Gwenaelle Le Pen, Julien Matricon, Thérèse M. Jay, Marie Odile Krebs

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Background: The development of new treatment alternatives for schizophrenia has been prevented by the unknown etiology of the illness and the divergence of results in the field. However, consistent neuropathological findings are emerging from anatomical areas known to be at the core of schizophrenia. If these deficiencies are replicated in animal models then such anomalies could become the target for a new generation of drugs. Objective: To determine if the methylazoxymethanol acetate (MAM) model, the heterozygote reeler mouse (HRM) and NMDA-antagonists treated rats replicate neuropathological deficits encountered in patients with schizophrenia and to establish if such changes could lead the search for developing novel treatment alternatives. Methods: Databases including MEDLINE, Cochrane and Ovid were searched; search terms included neuropathology, schizophrenia and animal models. Results/conclusions: NMDA-antagonist treated animals partially replicate schizophrenia anomalies in parvalbumin positive interneurons. In contrast, neuroanatomical deficiencies replicated by the MAM model and the HRM in the hippocampus and the prefrontal cortex seem promising targets for future pharmacological research in schizophrenia. Such neuroanatomical findings along with evidence from molecules and genes associated with schizophrenia suggest new drugs should aim to correct deficits in the formation of dendrites and axons that seems to be implicated in this illness pathophysiology.

Original languageEnglish (US)
Pages (from-to)257-278
Number of pages22
JournalExpert Opinion on Drug Discovery
Volume4
Issue number3
DOIs
StatePublished - Mar 2009

All Science Journal Classification (ASJC) codes

  • Drug Discovery

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