Egan M F, Hurd Y, Ferguson J, Bachus S E, Hamid E H, Hyde T M
Clinical Research Services, National Institute of Mental Health, NIMH Neuroscience Research Center at St. Elizabeths, Washington, DC 20032, USA.
Psychopharmacology (Berl). 1996 Oct;127(4):337-45. doi: 10.1007/s002130050095.
Late onset vacuous chewing movements (VCMs) from chronic neuroleptic treatment have been used as a rat model of tardive dyskinesia (TD). Early onset VCMs have also been observed, raising questions about the validity of this model. To assess the relationship between these two types of VCMs, pharmacological and neurochemical properties of early and late onset VCMs were compared. "Acute" VCMs were induced by daily intraperitoneal injections for 1-21 days. "Tardive" VCMs were induced by intramuscular injections of haloperidol decanoate every 3 weeks for 30 weeks followed by a 24-week withdrawal period. Suppression was attempted for both types of VCMs using several doses of intraperitoneal haloperidol. Striatonigral activation was assessed by measuring mRNA expression levels of the neuropeptides dynorphin and substance P using in situ hybridization histochemistry. Enkephalin mRNA was also measured as an index of striatopallidal activation. The results indicate that acute VCMs cannot be suppressed with increased doses of haloperidol and are associated with reduced dynorphin and substance P. This profile is similar to that seen with an animal model of parkinsonism. Tardive VCMs, in contrast, were markedly suppressed by haloperidol. They have previously been shown to be associated with increased striatonigral activation as indicated by increased dynorphin mRNA. Enkephalin mRNA was elevated following both short and long term treatment. Although superficially similar, acute and tardive VCMs appear to have different pharmacological and neurochemical profiles, suggesting they are related to acute extrapyramidal side effects and tardive dyskinesia, respectively.
慢性抗精神病药物治疗引发的迟发性空嚼运动（VCMs）已被用作迟发性运动障碍（TD）的大鼠模型。也观察到了早发性VCMs，这引发了对该模型有效性的质疑。为了评估这两种类型VCMs之间的关系，对早发性和迟发性VCMs的药理学和神经化学特性进行了比较。“急性”VCMs通过每日腹腔注射1 - 21天诱导产生。“迟发性”VCMs通过每3周肌肉注射癸酸氟哌啶醇，持续30周，随后停药24周诱导产生。尝试使用几种剂量的腹腔注射氟哌啶醇对两种类型的VCMs进行抑制。通过原位杂交组织化学测量神经肽强啡肽和P物质的mRNA表达水平来评估纹状体黑质激活。脑啡肽mRNA也作为纹状体苍白球激活的指标进行测量。结果表明，增加氟哌啶醇剂量不能抑制急性VCMs，且急性VCMs与强啡肽和P物质减少有关。这种情况与帕金森病动物模型所见相似。相比之下，迟发性VCMs被氟哌啶醇显著抑制。先前的研究表明，迟发性VCMs与强啡肽mRNA增加所表明的纹状体黑质激活增加有关。短期和长期治疗后脑啡肽mRNA均升高。尽管急性和迟发性VCMs表面上相似，但它们似乎具有不同的药理学和神经化学特征，这表明它们分别与急性锥体外系副作用和迟发性运动障碍有关。
