De Souza Ian E J, Dawson Niamh M, Clifford Jeremiah J, Waddington John L, Meredith Gloria E
Department of Anatomy, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
Psychopharmacology (Berl). 2003 Aug;169(1):28-34. doi: 10.1007/s00213-003-1466-2. Epub 2003 Jun 27.
Late-onset vacuous chewing movements (VCMs) arise in a significant proportion of rats treated chronically with conventional antipsychotic drugs. Given their common action to block dopamine D2-like receptors, VCMs may be related to changes in dopaminergic function; if so, other typical dopamine-mediated behaviours might be altered also.
To examine this hypothesis, behavioural repertoire was studied topographically over the course of chronic treatment and withdrawal.
Animals were injected with haloperidol decanoate 28 mg/kg IM, or vehicle, every 3 weeks for 27 weeks, and then maintained without treatment for a further 18 weeks. Immediately before each injection and during withdrawal, VCMs and other topographies of behaviour were assessed.
In both control and haloperidol-treated rats, exploratory behaviours declined over the study, indicating habituation effects. Conversely, VCMs emerged after 6 weeks of treatment with haloperidol and persisted after withdrawal; VCM and locomotion were not related, indicating that in treated rats, increased VCMs are not an artifact of reduced locomotion. Treated animals with VCMs evidenced increases in buccal tremor and grooming behaviour relative to those without VCMs, although no clear relationship to the emergence of VCMs was established; there were no material differences in any other topographies of behaviour.
The effect of long-term treatment with haloperidol to induce VCMs is not reflected in fundamental changes in dopamine-mediated behavioural topography but, rather, appears to affect neural mechanisms involved in orofacial movement preferentially.
在相当比例长期接受传统抗精神病药物治疗的大鼠中会出现迟发性空嚼运动(VCM)。鉴于它们都有阻断多巴胺D2样受体的共同作用,VCM可能与多巴胺能功能的变化有关;如果是这样,其他典型的多巴胺介导的行为可能也会改变。
为检验这一假设,在慢性治疗和撤药过程中对行为表现进行了地形学研究。
动物每3周接受一次28mg/kg肌肉注射癸酸氟哌啶醇或赋形剂,持续27周,然后在无治疗的情况下再维持18周。在每次注射前及撤药期间,评估VCM和其他行为表现。
在对照大鼠和接受氟哌啶醇治疗的大鼠中,探索行为在研究过程中均下降,表明存在习惯化效应。相反,氟哌啶醇治疗6周后出现VCM,并在撤药后持续存在;VCM与运动无关,表明在接受治疗的大鼠中,VCM增加并非运动减少的假象。与无VCM的动物相比,有VCM的接受治疗动物的颊部震颤和梳理行为增加,尽管未明确建立与VCM出现的关系;在任何其他行为表现方面均无实质性差异。
长期使用氟哌啶醇诱导VCM的作用并未反映在多巴胺介导的行为地形学的根本变化中,而是似乎优先影响参与口面部运动的神经机制。