Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11790, USA.
Synapse. 2010 Jul;64(7):503-10. doi: 10.1002/syn.20755.
Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [(3)H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.
外周和中枢给予瘦素已被证明可介导中枢多巴胺（DA）信号。瘦素受体缺失的啮齿动物纹状体中的 DA D2 受体（D2R）结合减少，与对照组相比具有独特的 DA 图谱。瘦素缺乏的小鼠在与奖励相关的脑区显示出增加的 DA 活性。本研究的目的是检查基础 D2R 结合差异是否导致瘦素缺乏 ob/ob 小鼠的表型行为，以及 D2R 结合是否在这些小鼠中对外周瘦素治疗有反应而改变。瘦素降低了 ob/ob 小鼠的体重、食物摄入量和血浆胰岛素浓度，但对野生型小鼠没有影响。ob/ob 和野生型小鼠之间的基底纹状体 D2R 结合（通过放射性自显影 [(3)H] spiperone 测量）没有差异，但对瘦素的反应却不同。在野生型小鼠中，瘦素降低了纹状体 D2R 结合，而在 ob/ob 小鼠中，瘦素增加了 D2R 结合。我们的发现进一步证明了瘦素调节纹状体中的 D2R 表达，并且这些作用是基因型/表型依赖性的。
