Progressive recruitment of cortical and striatal regions by inducible postsynaptic density transcripts after increasing doses of antipsychotics with different receptor profiles: Insights for psychosis treatment

Autor: Gianmarco Latte, Federica Marmo, Livia Avvisati, Rodolfo Rossi, Anna Eramo, Carmine Tomasetti, Elisabetta F. Buonaguro, Andrea de Bartolomeis, Felice Iasevoli
Přispěvatelé: DE BARTOLOMEIS, Andrea, Iasevoli, Felice, Marmo, Federica, Buonaguro, ELISABETTA FILOMENA, Eramo, Anna, Rossi, Rodolfo, Avvisati, Livia, Latte, Gianmarco, Tomasetti, Carmine
Rok vydání: 2015
Předmět:
Male
medicine.medical_treatment
Rats
Sprague-Dawley
Homer Scaffolding Proteins
AIDS-Related Complex
Haloperidol
Asenapine
Pharmacology (medical)
Membrane Protein
Cerebral Cortex
Homer Scaffolding Protein
Intracellular Signaling Peptides and Proteins
Oncogene Proteins v-fo
Psychiatry and Mental health
medicine.anatomical_structure
Neurology
Cerebral cortex
Psychology
Disks Large Homolog 4 Protein
Antipsychotic Agents
Protein Binding
medicine.drug
Psychosis
Bipolar disorder
Motor Activity
Statistics
Nonparametric
Dopamine receptor D2
medicine
Animals
RNA
Messenger
Antipsychotic
Biological Psychiatry
Early Growth Response Protein 1
Immediate-early gene
Pharmacology
Analysis of Variance
Dose-Response Relationship
Drug
Animal
Membrane Proteins
Post-Synaptic Density
medicine.disease
Corpus Striatum
Rats
Homer
Antipsychotic Agent
Oncogene Proteins v-fos
Settore MED/25
Gene Expression Regulation
Intracellular Signaling Peptides and Protein
Synaptic plasticity
Schizophrenia
Rat
Neurology (clinical)
Carrier Protein
Carrier Proteins
Neuroscience
Postsynaptic density
Zdroj: European Neuropsychopharmacology. 25:566-582
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2015.01.003
Popis: Antipsychotics may modulate the transcription of multiple gene programs, including those belonging to postsynaptic density (PSD) network, within cortical and subcortical brain regions. Understanding which brain region is activated progressively by increasing doses of antipsychotics and how their different receptor profiles may impact such an activation could be relevant to better correlate the mechanism of action of antipsychotics both with their efficacy and side effects. We analyzed the differential topography of PSD transcripts by incremental doses of two antipsychotics: haloperidol, the prototypical first generation antipsychotic with prevalent dopamine D2 receptors antagonism, and asenapine, a second generation antipsychotic characterized by multiple receptors occupancy. We investigated the expression of PSD genes involved in synaptic plasticity and previously demonstrated to be modulated by antipsychotics: Homer1a, and its related interacting constitutive genes Homer1b/c and PSD95, as well as Arc, C-fos and Zif-268, also known to be induced by antipsychotics administration. We found that increasing acute doses of haloperidol induced immediate-early genes (IEGs) expression in different striatal areas, which were progressively recruited by incremental doses with a dorsal-to-ventral gradient of expression. Conversely, increasing acute asenapine doses progressively de-recruited IEGs expression in cortical areas and increased striatal genes signal intensity. These effects were mirrored by a progressive reduction in locomotor animal activity by haloperidol, and an opposite increase by asenapine. Thus, we demonstrated for the first time that antipsychotics may progressively recruit PSD-related IEGs expression in cortical and subcortical areas when administered at incremental doses and these effects may reflect a fine-tuned dose-dependent modulation of the PSD.
Databáze: OpenAIRE
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