Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr
clozapine
haloperidol
hypokinetic movement disorders
olanzapine
phosphoThr75-Darpp-32
striatum
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
29 Sep 2023
29 Sep 2023
Historique:
received:
26
08
2023
revised:
16
09
2023
accepted:
19
09
2023
medline:
28
10
2023
pubmed:
28
10
2023
entrez:
28
10
2023
Statut:
epublish
Résumé
Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics are poorly understood. The present study aimed to determine the differential and long-lasting changes in FosB distribution and DARPP-32 phosphorylation in the striatum and nucleus accumbens (NAc) associated with chronic antipsychotic-induced EPS. Male C57Bl/6J mice received daily injections of Olanzapine (Olz, 15 mg/kg), Clozapine (Clz, 20 mg/kg), or Haloperidol (Hal, 1 mg/kg), for a period of 11 weeks with a 4-day withdrawal period before the last dosage. Catalepsy for detection of EPS, along with open-field and rotarod tests, were assessed as behavioral correlates of motor responses. Additionally, FosB and phosphorylated-DARPP-32 immunohistochemistry were examined in striatal regions after treatment. All antipsychotics produced catalepsy and reduced open-field exploration, such as impaired rota-rod performance after Olz and Hal. The washout period was critical for Clz-induced side effects reduction. Both Olz and Clz increased FosB in NAc Shell-region, and phosphoThr
Identifiants
pubmed: 37893051
pii: biomedicines11102677
doi: 10.3390/biomedicines11102677
pmc: PMC10604349
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : FAPESP
ID : 2015/02991-0
Organisme : CAPES
ID : 001
Organisme : Universidad de Santander
ID : 010-11
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