Powell Susan B, Lehmann-Masten Virginia D, Paulus Martin P, Gainetdinov Raul R, Caron Marc G, Geyer Mark A
Department of Psychiatry 0804, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Psychopharmacology (Berl). 2004 May;173(3-4):310-7. doi: 10.1007/s00213-003-1765-7. Epub 2004 Jan 28.
Mice lacking the gene for the dopamine transporter (DAT) show a unique behavioral phenotype characterized by locomotor hyperactivity and repetitive circling in a novel environment. The hyperactivity of DAT (-/-) mice can be attenuated by psychostimulants and by serotonin uptake inhibitors, suggesting an important role for serotonin in the attenuation of locomotor hyperactivity in these mice.
These studies characterized the effects of 3,4-methylenedioxy-N-methylamphetamine (MDMA), a serotonin releaser, on the amount and patterns of locomotor activity in DAT (+/+) and (-/-) mice. We compared the locomotor patterns produced by MDMA to those observed in DAT (-/-) mice, and examined whether MDMA altered the hyperactivity and perseverative locomotor patterns in DAT (-/-) mice.
The effects of MDMA (10, 30 mg/kg) on locomotor activity in DAT (+/+) mice were measured for 90 min in a video tracker system to determine the optimal dose for subsequent studies in DAT (+/+) and (-/-) mice. The effects of 20 mg/kg MDMA on patterns of locomotor activity in DAT (+/+) and (-/-) mice were measured for 90 min.
In DAT (+/+) mice, MDMA increased locomotor activity and induced repetitive straight movement patterns. In DAT (-/-) mice, however, MDMA (20 mg/kg) attenuated the characteristic locomotor hyperactivity seen in these mice. In contrast, MDMA potentiated the thigmotaxis and decreased entropy observed in the DAT (-/-) mice.
The effects of MDMA observed here demonstrate that the different aspects of the abnormal locomotor behavior exhibited by DAT (-/-) mice can be independently manipulated by pharmacological treatments.
缺乏多巴胺转运体（DAT）基因的小鼠表现出独特的行为表型，其特征为在新环境中运动亢进和反复转圈。DAT（-/-）小鼠的运动亢进可被精神兴奋剂和5-羟色胺摄取抑制剂减弱，这表明5-羟色胺在减弱这些小鼠的运动亢进中起重要作用。
这些研究表征了5-羟色胺释放剂3,4-亚甲基二氧基-N-甲基苯丙胺（摇头丸）对DAT（+/+）和（-/-）小鼠运动活动量及模式的影响。我们将摇头丸产生的运动模式与在DAT（-/-）小鼠中观察到的模式进行比较，并检查摇头丸是否改变了DAT（-/-）小鼠的运动亢进和持续性运动模式。
在视频跟踪系统中测量摇头丸（10、30mg/kg）对DAT（+/+）小鼠运动活动的影响90分钟，以确定后续对DAT（+/+）和（-/-）小鼠研究的最佳剂量。测量20mg/kg摇头丸对DAT（+/+）和（-/-）小鼠运动活动模式的影响90分钟。
在DAT（+/+）小鼠中，摇头丸增加了运动活动并诱导了反复直线运动模式。然而，在DAT（-/-）小鼠中，摇头丸（20mg/kg）减弱了这些小鼠中特有的运动亢进。相反，摇头丸增强了DAT（-/-）小鼠中观察到的趋触性并降低了熵。
此处观察到的摇头丸的作用表明，DAT（-/-）小鼠表现出的异常运动行为的不同方面可通过药物治疗独立操控。
