Getulio Nicola Bressan, Talita Rodrigues, Maria Eduarda Brandli da Silva, Maria Rosa Chitolina Schetinger, Rahisa Scussel, Ricardo Andrez Machado-de-Ávila, Jéssica da Silva Abel, Roselei Fachinetto
{"title":"急性氟哌啶醇治疗对高VCMs和低VCMs大鼠多巴胺能标记物、GAD67和A2A受体的影响","authors":"Getulio Nicola Bressan, Talita Rodrigues, Maria Eduarda Brandli da Silva, Maria Rosa Chitolina Schetinger, Rahisa Scussel, Ricardo Andrez Machado-de-Ávila, Jéssica da Silva Abel, Roselei Fachinetto","doi":"10.1007/s11064-024-04275-w","DOIUrl":null,"url":null,"abstract":"<div><p>Vacuous chewing movements (VCM) have been utilized as an experimental model of orofacial dyskinesia (OD) in rodents to study the underlying molecular mechanisms related to tardive dyskinesia (TD). This study aimed to investigate if the acute treatment with haloperidol can alter components of the dopaminergic synapse or its modulators such as glutamic acid decarboxylase (GAD<sub>67</sub>) and adenosine 2A (A<sub>2A</sub>) receptor. Furthermore, to evaluate if changes in molecular markers are associated with the number of VCMs induced by haloperidol in rats it is proposing a method to classify the animals into High and Low VCM groups. Here, we treated rats with haloperidol decanoate (single injection, intramuscularly, 28 mg/Kg of unconjugated haloperidol) and evaluated the number of VCMs after 4 weeks. Haloperidol-treated rats were divided into three groups (Low, High, and Spontaneous VCM) according to the evaluation of the VCM profile proposed here. After, dopamine (DA) levels, monoamine oxidase (MAO) activity, and the immunoreactivity of tyrosine hydroxylase (TH), dopamine transporter (DAT), D<sub>2</sub> receptor, GAD<sub>67</sub>, and A<sub>2A</sub> were determined in brain structures. No significant differences were found in DA levels, MAO activity, and immunoreactivity of the TH, DAT, D<sub>2</sub> receptor, GAD<sub>67</sub>, and A<sub>2A</sub> receptor in brain structures. VCM intensity was correlated with TH immunoreactivity in <i>Sn</i> in the High VCM group while it was inversely correlated with the immunoreactivity of the A<sub>2A</sub> receptor in the striatum of the Spontaneous VCM group. Other significant correlations were found considering the VCM profile suggesting that High VCM after acute haloperidol treatment seems to be associated with the lack of ability to reorganize the neurotransmission in the nigrostriatal pathway. Further studies could clarify the main targets involved in the motor side effects of antipsychotics. The present study demonstrated an easy way to separate the animals into High and Low VCMs.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Acute Haloperidol Treatment on Dopaminergic Markers, GAD67, and A2A Receptors in Rats with High and Low VCMs\",\"authors\":\"Getulio Nicola Bressan, Talita Rodrigues, Maria Eduarda Brandli da Silva, Maria Rosa Chitolina Schetinger, Rahisa Scussel, Ricardo Andrez Machado-de-Ávila, Jéssica da Silva Abel, Roselei Fachinetto\",\"doi\":\"10.1007/s11064-024-04275-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Vacuous chewing movements (VCM) have been utilized as an experimental model of orofacial dyskinesia (OD) in rodents to study the underlying molecular mechanisms related to tardive dyskinesia (TD). This study aimed to investigate if the acute treatment with haloperidol can alter components of the dopaminergic synapse or its modulators such as glutamic acid decarboxylase (GAD<sub>67</sub>) and adenosine 2A (A<sub>2A</sub>) receptor. Furthermore, to evaluate if changes in molecular markers are associated with the number of VCMs induced by haloperidol in rats it is proposing a method to classify the animals into High and Low VCM groups. Here, we treated rats with haloperidol decanoate (single injection, intramuscularly, 28 mg/Kg of unconjugated haloperidol) and evaluated the number of VCMs after 4 weeks. Haloperidol-treated rats were divided into three groups (Low, High, and Spontaneous VCM) according to the evaluation of the VCM profile proposed here. After, dopamine (DA) levels, monoamine oxidase (MAO) activity, and the immunoreactivity of tyrosine hydroxylase (TH), dopamine transporter (DAT), D<sub>2</sub> receptor, GAD<sub>67</sub>, and A<sub>2A</sub> were determined in brain structures. No significant differences were found in DA levels, MAO activity, and immunoreactivity of the TH, DAT, D<sub>2</sub> receptor, GAD<sub>67</sub>, and A<sub>2A</sub> receptor in brain structures. VCM intensity was correlated with TH immunoreactivity in <i>Sn</i> in the High VCM group while it was inversely correlated with the immunoreactivity of the A<sub>2A</sub> receptor in the striatum of the Spontaneous VCM group. Other significant correlations were found considering the VCM profile suggesting that High VCM after acute haloperidol treatment seems to be associated with the lack of ability to reorganize the neurotransmission in the nigrostriatal pathway. Further studies could clarify the main targets involved in the motor side effects of antipsychotics. The present study demonstrated an easy way to separate the animals into High and Low VCMs.</p></div>\",\"PeriodicalId\":719,\"journal\":{\"name\":\"Neurochemical Research\",\"volume\":\"50 1\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurochemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11064-024-04275-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-024-04275-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Effects of Acute Haloperidol Treatment on Dopaminergic Markers, GAD67, and A2A Receptors in Rats with High and Low VCMs
Vacuous chewing movements (VCM) have been utilized as an experimental model of orofacial dyskinesia (OD) in rodents to study the underlying molecular mechanisms related to tardive dyskinesia (TD). This study aimed to investigate if the acute treatment with haloperidol can alter components of the dopaminergic synapse or its modulators such as glutamic acid decarboxylase (GAD67) and adenosine 2A (A2A) receptor. Furthermore, to evaluate if changes in molecular markers are associated with the number of VCMs induced by haloperidol in rats it is proposing a method to classify the animals into High and Low VCM groups. Here, we treated rats with haloperidol decanoate (single injection, intramuscularly, 28 mg/Kg of unconjugated haloperidol) and evaluated the number of VCMs after 4 weeks. Haloperidol-treated rats were divided into three groups (Low, High, and Spontaneous VCM) according to the evaluation of the VCM profile proposed here. After, dopamine (DA) levels, monoamine oxidase (MAO) activity, and the immunoreactivity of tyrosine hydroxylase (TH), dopamine transporter (DAT), D2 receptor, GAD67, and A2A were determined in brain structures. No significant differences were found in DA levels, MAO activity, and immunoreactivity of the TH, DAT, D2 receptor, GAD67, and A2A receptor in brain structures. VCM intensity was correlated with TH immunoreactivity in Sn in the High VCM group while it was inversely correlated with the immunoreactivity of the A2A receptor in the striatum of the Spontaneous VCM group. Other significant correlations were found considering the VCM profile suggesting that High VCM after acute haloperidol treatment seems to be associated with the lack of ability to reorganize the neurotransmission in the nigrostriatal pathway. Further studies could clarify the main targets involved in the motor side effects of antipsychotics. The present study demonstrated an easy way to separate the animals into High and Low VCMs.
期刊介绍：
Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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