| Autor: |
Prieto SG; Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, Brazil., Almeida MC; Center for Natural and Human Sciences, Federal University of ABC, São Bernardo do Campo 09606-045, SP, Brazil., Silva JCS; Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, Brazil., Del-Bel E; Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 05508-000, SP, Brazil., Echeverry MB; Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, Brazil.; Neuroscience Laboratory, School of Medicine, Universidad de Santander (UDES), Bucaramanga 39006-39005, Santander, Colombia. |
| Abstrakt: |
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 34 -DARPP-32 in NAc. Only Clz reduced phosphoThr 75 -DARPP-32 in the dorsal striatum and showed FosB/phosphoThr 34 -Darpp-32-ir in the NAc Core region. This study provides evidence that atypical antipsychotics such as Olz and Clz also give rise to EPS effects frequently associated with a cumulative dosage of typical neuroleptics such as Hal. Nevertheless, FosB/phosphoThr 34 -Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition. |
