Marmo, Federica (2015) Switching antipsychotics: how and where a prolonged treatment with a typical antipsychotic affects the topography of postsynaptic density gene expression induced by an atypical antipsychotic. Relevance for pychosis treatment. [Tesi di dottorato]

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Typical and atypical antipsychotics can be characterized at preclinical levels by differential induction of several Immediate Early Genes localized at cortical and subcortical regions related to pathogenesis of psychiatric disorders and antipsychotics action. So, genes expression. Molecular imaging under different treatment paradigms could be considered a sensitive molecular tool to investigate where drugs act, predicting, with a translational approach a clinical outcome. In clinical practice psychiatrists frequently switch from one antipsychotic to another with different receptorial profile when patients show poor or no treatment response or intolerable adverse effect, but the post-switch antipsychotics response is different compared to drug naïve patients. Neuroimaging studies highlighted morphological and molecular changes after long-term administration in brain regions affected by antipsychotics, resulting in unexpected clinical outcome. In our study we analyze Immediate Early Genes expression of proteins localized ad Postsynaptic Density (PSD), where dopaminergic and glutamatergic transmission converging, in an animal model of switching. Thus we highlight that first chronic treatment with strong D2 blocker affects genes expression induced by second chronic treatment with antipsychotic characterized by a different receptorial profile, confirming, at molecular level, what happens in clinical practice and giving new challenges towards antipsychotic mechanism of action.

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