Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake
Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake
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DOI：
10.1152/ajpregu.00092.2002
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发表时间：
2002-10-01
影响因子：
2.8
通讯作者：
Zhang, LH
中科院分区：
文献类型：
--
作者：
Fetissov, SO;Meguid, MM;Zhang, LH
正如先前的微透析研究所揭示的那样，肥胖与瘦Zucker大鼠的下丘脑中基础和食物摄入伴随的多巴胺释放显著不同。在本研究中，我们确定了多巴胺能受体是否也在肥胖中受损。应用RT-PCR技术研究了肥胖和消瘦Zucker大鼠下丘脑腹内侧区（VMH）、下丘脑外侧区（LHA）和腺垂体（AH）多巴胺能D-1和D-2受体mRNA的表达。在肥胖Zucker大鼠中，我们发现与瘦大鼠相比，VMH和AH中的D-1受体mRNA上调，LHA中的D-1受体mRNA下调，而VMH和LHA中的D-2受体mRNA下调，但AH中没有变化。免疫组化结果显示，肥胖大鼠室旁核D-1受体染色增强。我们选择VMH来测试所观察到的肥胖大鼠多巴胺受体表达的变化是否诱导了对多巴胺的行为敏化，如通过暴食所表达的。禁食过夜的大鼠接受单次VMH注射（10 nmol）舒必利（D-2受体拮抗剂）或生理盐水作为对照，然后提供食物并测量1小时的食物摄入量。肥胖大鼠注射舒必利后的食物摄入量大于注射生理盐水后的食物摄入量，但在瘦大鼠中没有差异。我们的数据表明，下调D-2受体在下丘脑至少在VMH诱导行为敏感化有大量的食物。低D-2受体表达可能是肥胖大鼠在食物摄入过程中观察到的多巴胺过度释放和多巴胺饱腹感反馈效应降低的原因。D-1受体在VMH的高水平表达和LHA的低水平表达也可能有助于肥胖大鼠的特定进食模式，表现为大量膳食和低膳食数量。
As revealed by previous microdialysis studies, basal and food intake-accompanied dopamine release significantly differs in the hypothalamus of obese vs. lean Zucker rats. In the present study, we determined whether dopaminergic receptors are also compromised in obesity. Dopaminergic D-1 and D-2 receptor mRNA expression was studied in the ventromedial hypothalamus (VMH), lateral hypothalamic area (LHA), and the adenohypophysis (AH) of obese and lean Zucker rats using RT-PCR technique. In obese Zucker rats, we found an upregulation of D-1 receptor mRNA in the VMH and AH and a downregulation in the LHA, whereas D-2 receptor mRNA was downregulated in both the VMH and LHA, but not changed in the AH, compared with lean rats. Also, an increase of D-1 receptor staining was seen in the paraventricular nucleus of obese rats by immunohistochemistry. We selected the VMH to test if the observed changes in the dopamine receptor expression of obese rats induce behavioral sensitization to dopamine as expressed by hyperphagia. The overnight food-deprived rats received a single VMH injection (10 nmol) of sulpiride (D-2 receptor antagonist) or saline as control, then food was provided and 1-h food intake was measured. Food intake after sulpiride vs. saline injection was greater in obese rats but was not different in lean rats. Our data suggest that downregulation of D-2 receptor in the hypothalamus at least in the VMH induces behavior sensitization for having large meals. Low D-2 receptor expression may be causal for an exaggerated dopamine release observed in obese rats during food ingestion and for reduced satiety feedback effect of dopamine. High level of D-1 receptor expression in the VMH and low in the LHA may also contribute to the specific feeding pattern in obese rats represented by large meal size and low meal number.