Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.
Animals
Antipsychotic Agents
/ administration & dosage
Brain
/ drug effects
Drug Administration Schedule
Genes, Immediate-Early
/ drug effects
Male
Piperazines
/ administration & dosage
Piperidines
/ administration & dosage
Rats
Rats, Sprague-Dawley
Receptors, Dopamine
/ metabolism
Schizophrenia
/ drug therapy
Stress, Psychological
/ drug therapy
Forced swim stress
Hippocampus
Immediate early genes
Neuronal activity
Prefrontal cortex
Rats
Real-time PCR
Schizophrenia
Striatum
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
16
01
2020
accepted:
27
02
2020
pubmed:
17
4
2020
medline:
30
9
2020
entrez:
17
4
2020
Statut:
ppublish
Résumé
Patients diagnosed with schizophrenia typically receive life-long treatments with antipsychotic drugs (APDs). However, the impact of chronic APDs treatment on neuroplastic mechanisms in the brain remains largely elusive. Here, we focused on blonanserin, a second-generation antipsychotic (SGA) that acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors, and represents an important tool for the treatment of schizophrenia. We used rats to investigate the ability of chronic treatment blonanserin to modulate the activity of brain structures relevant for schizophrenia, under baseline conditions or in response to an acute forced swim session (FSS). We measured the expression of different immediate early genes (IEGs), including c-Fos, Arc/Arg 3.1, Zif268 and Npas4. Blonanserin per se produced limited changes in the expression of these genes under basal conditions, while, as expected, FSS produced a significant elevation of IEGs transcription in different brain regions. The response of blonanserin-treated rats to FSS show anatomical and gene-selective differences. Indeed, the upregulation of IEGs was greatly reduced in the striatum, a brain structure enriched in dopamine receptors, whereas the upregulation of some genes (Zif268, Npas4) was largely preserved in other regions, such as the prefrontal cortex and the ventral hippocampus. Taken together, our findings show that chronic exposure to blonanserin modulates selective IEGs with a specific anatomical profile. Moreover, the differential activation of specific brain regions under challenging conditions may contribute to specific clinical features of the drug.
Identifiants
pubmed: 32296859
doi: 10.1007/s00213-020-05498-9
pii: 10.1007/s00213-020-05498-9
doi:
Substances chimiques
Antipsychotic Agents
0
Piperazines
0
Piperidines
0
Receptors, Dopamine
0
blonanserin
AQ316B4F8C
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1783-1793Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PRIN 2017AY8BP4
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PON "Ricerca e Innovazione" PerMedNet project ARS01_01226
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