Powell Susan B, Young Jared W, Ong Jacob C, Caron Marc G, Geyer Mark A
aDepartment of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, USA.
Behav Pharmacol. 2008 Sep;19(5-6):562-5. doi: 10.1097/FBP.0b013e32830dc110.
Sensorimotor gating disruptions are seen in various psychiatric illnesses with putatively different pathologies, including schizophrenia and bipolar disorder. Interestingly, mice lacking the dopamine (DA) transporter (DAT) gene display markedly increased levels of DA, deficits in sensorimotor gating, and hyperactivity relative to wild-type mice. Atypical antipsychotics are effective treatments of schizophrenia and manic symptoms, presumably in part by antagonizing DA receptors. Here we report that treatment with clozapine (3 mg/kg) or quetiapine (2.5 mg/kg) attenuated prepulse inhibition deficits in male DAT knockout mice. Thus male DAT knockout mice may provide a useful animal model for predicting the efficacy of novel drugs in treating psychiatric illnesses characterized by a dysregulated DA system.
感觉运动门控障碍在各种具有不同病理特征的精神疾病中都有出现，包括精神分裂症和双相情感障碍。有趣的是，缺乏多巴胺（DA）转运体（DAT）基因的小鼠相对于野生型小鼠，其DA水平显著升高，感觉运动门控存在缺陷，且表现出多动症状。非典型抗精神病药物是治疗精神分裂症和躁狂症状的有效药物，推测部分原因是通过拮抗DA受体。在此我们报告，用氯氮平（3毫克/千克）或喹硫平（2.5毫克/千克）治疗可减轻雄性DAT基因敲除小鼠的前脉冲抑制缺陷。因此，雄性DAT基因敲除小鼠可能为预测新型药物治疗以DA系统失调为特征的精神疾病的疗效提供有用的动物模型。
