Korea University, Seoul, South Korea.
Biochem Biophys Res Commun. 2010 Mar 5;393(2):235-41. doi: 10.1016/j.bbrc.2010.01.108. Epub 2010 Feb 1.
Many atypical antipsychotic drugs cause weight gain, but the mechanism of this weight gain is unclear. To dissect the role of the dopamine D2 receptor (D2R), an important receptor in the pharmacology of antipsychotic drugs, we analyzed the effect of olanzapine, risperidone, and ziprasidone on changes in body weight and food intake in male wild-type (WT) and D2R knockout (D2R(-/-)) mice. The oral delivery of atypical antipsychotics, olanzapine (5 and 10mg/kg), risperidone (0.1 and 1.0mg/kg) and ziprasidone (10 and 20mg/kg) in both strains mice for 2 weeks suppressed body weight gain, except for olanzapine treatment in D2R(-/-) mice. Olanzapine treatment suppressed body weight gain and decreased food intake in WT mice, but also reduced fat body mass and locomotor activity, whereas D2R(-/-) mice did not show these changes. Ziprasidone and risperidone treatment produced similar responses in WT and D2R(-/-) mice. These data suggest the involvement of D2R in the effect of olanzapine on metabolic regulation. Further studies are required to explore the implications of D2R activity in antipsychotic-mediated metabolic complications.
许多非典型抗精神病药物会导致体重增加，但这种体重增加的机制尚不清楚。为了剖析多巴胺 D2 受体（D2R）的作用，该受体是抗精神病药物药理学中的一个重要受体，我们分析了奥氮平、利培酮和齐拉西酮对雄性野生型（WT）和 D2R 敲除（D2R(-/-)）小鼠体重和食物摄入量变化的影响。非典型抗精神病药物奥氮平（5 和 10mg/kg）、利培酮（0.1 和 1.0mg/kg）和齐拉西酮（10 和 20mg/kg）通过口服给药，在两种品系的小鼠中连续治疗 2 周，均能抑制体重增加，除了奥氮平在 D2R(-/-)小鼠中的治疗作用。奥氮平治疗抑制 WT 小鼠的体重增加和食物摄入，但也降低了脂肪体重和运动活性，而 D2R(-/-)小鼠则没有这些变化。齐拉西酮和利培酮治疗在 WT 和 D2R(-/-)小鼠中产生了类似的反应。这些数据表明 D2R 参与了奥氮平对代谢调节的影响。需要进一步的研究来探讨 D2R 活性在抗精神病药物引起的代谢并发症中的意义。
