Roseberry Aaron G, Painter Tammie, Mark Gregory P, Williams John T
The Vollum Institute, Portland, Oregon 97239, USA.
J Neurosci. 2007 Jun 27;27(26):7021-7. doi: 10.1523/JNEUROSCI.1235-07.2007.
An increasing number of studies indicate that leptin can regulate the activity of the mesolimbic dopamine system. The objective of this study was to examine the regulation of the activity of dopamine neurons by leptin. This was accomplished by examining the dopamine D2 receptor-mediated synaptic current that resulted from somatodendritic release of dopamine in brain slices taken from mice that lacked leptin (Lep(ob/ob) mice). Under control conditions, the amplitude and kinetics of the IPSC in wild-type and Lep(ob/ob) mice were not different. However, in the presence of forskolin or cocaine, the facilitation of the dopamine IPSC was significantly reduced in Lep(ob/ob) mice. The application of L-3,4-dihydroxyphenylalanine (L-DOPA) increased the IPSC in Lep(ob/ob) mice significantly more than in wild-type animals and fully restored the responses to both forskolin and cocaine. Treatment of Lep(ob/ob) mice with leptin in vivo fully restored the cocaine-induced increase in the IPSC to wild-type levels. These results suggest that there is a decrease in the content of somatodendritic vesicular dopamine in the Lep(ob/ob) mice. The release of dopamine from terminals may be less affected in the Lep(ob/ob) mice, because the cocaine-induced rise in dopamine in the ventral striatum was not statistically different between wild-type and Lep(ob/ob) mice. In addition, the relative increase in cocaine-induced locomotion was similar for wild-type and Lep(ob/ob) mice. These results indicate that, although basal release is not altered, the amount of dopamine that can be released is reduced in Lep(ob/ob) mice.
越来越多的研究表明，瘦素可调节中脑边缘多巴胺系统的活性。本研究的目的是检测瘦素对多巴胺能神经元活性的调节作用。这是通过检测在缺乏瘦素的小鼠（Lep(ob/ob)小鼠）脑片中，由多巴胺的树突体释放所产生的多巴胺D2受体介导的突触电流来实现的。在对照条件下，野生型和Lep(ob/ob)小鼠中抑制性突触后电流（IPSC）的幅度和动力学并无差异。然而，在存在福斯可林或可卡因的情况下，Lep(ob/ob)小鼠中多巴胺IPSC的易化作用显著降低。给予左旋多巴（L-DOPA）后，Lep(ob/ob)小鼠的IPSC增加幅度显著大于野生型动物，并且完全恢复了对福斯可林和可卡因的反应。在体内用瘦素处理Lep(ob/ob)小鼠，可使可卡因诱导的IPSC增加完全恢复到野生型水平。这些结果表明，Lep(ob/ob)小鼠的树突体囊泡多巴胺含量减少。Lep(ob/ob)小鼠中多巴胺从终末的释放可能受影响较小，因为野生型和Lep(ob/ob)小鼠腹侧纹状体中可卡因诱导的多巴胺升高在统计学上并无差异。此外，野生型和Lep(ob/ob)小鼠中可卡因诱导的运动相对增加相似。这些结果表明，尽管基础释放未改变，但Lep(ob/ob)小鼠中可释放的多巴胺量减少。
