Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens
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 a...
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2677 |
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| author | Sonia G. Prieto Maria Camila Almeida João C. S. Silva Elaine Del-Bel Marcela B. Echeverry |
| author_facet | Sonia G. Prieto Maria Camila Almeida João C. S. Silva Elaine Del-Bel Marcela B. Echeverry |
| author_sort | Sonia G. Prieto |
| collection | DOAJ |
| description | 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<sup>34</sup>-DARPP-32 in NAc. Only Clz reduced phosphoThr<sup>75</sup>-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr<sup>34</sup>-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<sup>34</sup>-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition. |
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| language | English |
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| publishDate | 2023-09-01 |
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| spelling | doaj.art-b0a621e871fb41b39da7973a9216eafd2023-11-19T15:45:30ZengMDPI AGBiomedicines2227-90592023-09-011110267710.3390/biomedicines11102677Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus AccumbensSonia G. Prieto0Maria Camila Almeida1João C. S. Silva2Elaine Del-Bel3Marcela B. Echeverry4Center for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, BrazilCenter for Natural and Human Sciences, Federal University of ABC, São Bernardo do Campo 09606-045, SP, BrazilCenter for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, BrazilDepartment of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto 05508-000, SP, BrazilCenter for Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo 09606-045, SP, BrazilExtrapyramidal 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<sup>34</sup>-DARPP-32 in NAc. Only Clz reduced phosphoThr<sup>75</sup>-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr<sup>34</sup>-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<sup>34</sup>-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition.https://www.mdpi.com/2227-9059/11/10/2677hypokinetic movement disordersolanzapineclozapinehaloperidolstriatumphosphoThr<sup>75</sup>-Darpp-32 |
| spellingShingle | Sonia G. Prieto Maria Camila Almeida João C. S. Silva Elaine Del-Bel Marcela B. Echeverry Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens Biomedicines hypokinetic movement disorders olanzapine clozapine haloperidol striatum phosphoThr<sup>75</sup>-Darpp-32 |
| title | Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens |
| title_full | Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens |
| title_fullStr | Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens |
| title_full_unstemmed | Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens |
| title_short | Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr<sup>34</sup>-DARPP-32 in Nucleus Accumbens |
| title_sort | extrapyramidal side effects with chronic atypical antipsychotic can be predicted by labeling pattern of fosb and phosphothr sup 34 sup darpp 32 in nucleus accumbens |
| topic | hypokinetic movement disorders olanzapine clozapine haloperidol striatum phosphoThr<sup>75</sup>-Darpp-32 |
| url | https://www.mdpi.com/2227-9059/11/10/2677 |
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