The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats
The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats
复制标题
多巴胺D2受体占据与大鼠空性咀嚼运动综合征的关系
作者：
P. Turrone;G. Remington;S. Kapur;J. Nobrega
Abstract
Rationale. A dose–response relationship between dopamine D2 occupancy and acute extrapyramidal symptoms (EPS) has been well established. However, the link with the induction of tardive dyskinesia (TD) is less clear.
Objectives. To ascertain the nature and extent of D2 receptor occupancy effects on haloperidol-induced vacuous chewing movements (VCMs) in a rat model of TD.
Methods. Groups of eight rats received haloperidol decanoate injections corresponding to daily doses of 0, 0.08, 0.17, 0.33, or 1 mg/kg for 10–12 weeks. VCMs were measured on a weekly basis and D2 occupancy levels were measured in vivo using [3H]-raclopride at the end of the experiment.
Results. Final VCM scores were significantly different between haloperidol doses (P=0.001). Moderate but significant correlations were found between dose and average VCM scores (r=0.69, P<0.001) and between D2 occupancy and average VCM scores (r=0.65, P<0.001). The rats that developed the VCM syndrome (≥8 VCMs) had higher occupancies than rats that did not. Of the rats with an occupancy above 70%, 63% developed VCMs, compared with 37% of the rats with D2 occupancy below that.
Conclusions. These results indicate that chronic haloperidol induces VCMs in a dose-dependent manner, with doses leading to high D2 occupancy increasing the likelihood of emergence of the VCM syndrome. While a certain level of D2 occupancy may be necessary for inducing VCMs, it is not sufficient in and of itself to induce the VCM syndrome.
影响因子：
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作者：
L. Farde;A. Nordström;F. Wiesel;S. Pauli;C. Halldin;G. Sedvall
通讯作者：
L. Farde;A. Nordström;F. Wiesel;S. Pauli;C. Halldin;G. Sedvall
整合迟发性运动障碍的发病率和患病率。
影响因子：
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作者：
Kane,JM;Woerner,M;Borenstein,M;Wegner,J;Lieberman,J
通讯作者：
Lieberman,J
精神抑制药剂量和血浆水平在精神病药物治疗中的意义。
影响因子：
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作者：
Baldessarini,RJ;Cohen,BM;Teicher,MH
通讯作者：
Teicher,MH