title: Re-arrangements of gene transcripts at glutamatergic synapses after prolonged treatments with antipsychotics: A putative link with synaptic remodeling.
abstract: The postsynaptic density (PSD) represents a site of dopamine-glutamate integration. Despite multiple evidence of PSD involvement in antipsychotic-induced synaptic changes, there are no direct head-to-head comparisons of the effects at the PSD of antipsychotics with different receptor profile and at different doses after chronic administration.
  
  
  
  Molecular imaging of gene expression was used to investigate whether chronic treatment with first and second generation antipsychotics (haloperidol, asenapine and olanzapine) may induce changes in the expression levels of PSD transcripts involved in schizophrenia pathophysiology, i.e. Homers, Shank1, PSD-95 and Arc.
  
  
  
  Genes' expression patterns were differentially modulated after chronic administration of typical and atypical antipsychotics as well as by the same compound administered at different doses. Antipsychotic treatment reduced gene expression in cortical regions, while Homer1a was still induced in striatum by haloperidol even after prolonged treatment. Moreover, chronic treatments appeared to cause a "de-recruitment" of brain regions demonstrated to be activated in acute treatments, with a prominent effect in the cortex rather than in striatum.
  
  
  
  These results let hypothesize that prolonged antipsychotic treatment may trigger a set of plastic changes involving scaffolding and effector molecules causing a possible re-arrangement of PSD transcripts in brain regions relevant to schizophrenia pathophysiology.
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Elisabetta Filomena
authors.initials: EF
authors.lastname: Buonaguro
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marmo
authors.affiliation: Lundbeck LLC, Deerfield, IL, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Eramo
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Latte
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Avagliano
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, University of Naples Federico II, Italy. Electronic address: adebarto@unina.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003986:Dibenzocycloheptenes; D000076122:Disks Large Homolog 4 Protein / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D000077152:Olanzapine; D057907:Post-Synaptic Density / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D006576:Heterocyclic Compounds, 4 or More Rings; D009419:Nerve Tissue Proteins; C120531:Shank1 protein, rat; D001569:Benzodiazepines; D006220:Haloperidol; C522667:asenapine; D000077152:Olanzapine
keywords: Atypical antipsychotic; Brain imaging; PSD-95; Schizophrenia; Shank