期刊
NEUROREPORT
卷 19, 期 11, 页码 1137-1140出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0b013e3283063183
关键词
cocaine; dopamine transporter; knockin mice; stereotypy
资金
- NIDA NIH HHS [R01 DA014610, R01 DA014610-05, R01 DA014610-06A2, DA 014610, R01 DA014610-04S1] Funding Source: Medline
The primary mechanism by which cocaine induces stereotypy has been difficult to discern because cocaine has three high-affinity targets: the reuptake transporters for dopamine (DAT), norepinephrine, and serotonin. To dissect out the role of DAT in cocaine effects, we generated a knock-in mouse line with a cocaine-insensitive DAT (DAT-CI mice). DAT-CI mice provide a powerful tool that can directly test whether DAT inhibition is important for cocaine-induced stereotypy. We found that acute cocaine failed to produce stereotypy in DAT-CI mice. In fact, 40 mg/kg cocaine suppressed stereotypy in DAT-CI mice but produced profound stereotypy in wild-type mice. These findings suggest that DAT inhibition is necessary for cocaine-induced stereotypy. Furthermore, mechanisms independent of DAT inhibition appear to inhibit stereotypy. NeuroReport 19:1137-1140 (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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