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The involvement of the dopamine-3 receptor in the regulation and reward of food intake.

机译:多巴胺3受体参与食物摄入的调节和奖励。

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摘要

The DA receptors (DA-R) have been identified as potential targets for understanding processing of reward related behavior. The dopamine-3 receptor (D3-R) is expressed in the midbrain dopaminergic circuitry suggesting DA signaling at the D3-R may be vital to inhibition of reward processing. Mice lacking the D3-R (D3-R −/−) and wild-types (D3-R +/+) were given 3-month access to standard rodent chow or a preferable, high-fat (HF) diet. Following 3-months of access, mice were sacrificed and body weight, adiposity, food intake, plasma insulin and leptin, and metabolic measures were evaluated. D3-R −/− became obese on the preferable, HF diet but lacked an overt food intake phenotype. Thus, it was hypothesized that signaling at the D3-R enables an animal to integrate signals about peripheral energy availability and adjust food intake appropriately. Mercaptoacetate (MA), 2-deoxy-d-glucose (2-DG) and insulin were ineffective at increasing food intake in D3-R −/− mice, however peripheral glucose and fatty acids were elevated normally in response to the drugs. In contrast, the mutant mice were hyper-responsive to the anorectic effects of leptin and amylin. To further characterize reward-related behavior the D3-R −/− and +/+ mice were given access to increasing concentrations of ethanol. Ethanol intake is of interest because dopaminergic circuitry has been hypothesized to mediate consumption and is a caloric source with psycho-pharmacological properties. There was a genotypic based increased consumption by the D3-R −/− mice. To assess the hypothesized inhibitory role of the D3-R on food intake we administered the D3-R agonist (7-OH-DPAT) to rats with access to chow or HF diet in three different feeding regimens of varying levels of deprivation. In a final group of experiments animals with access to chow or HF diet were food restricted. On the test day 7-OH-DPAT was administered to animals that received the diet that was expected or the diet that violated expectancy (positive and negative expectancy). 7-OH-DPAT reduced intake of the positive contrast without reducing intake in the other conditions. To characterize central populations of D3-Rs that may influence this effect 7-OH-DPAT was administered directly into the nucleus accumbens (NAcc) or the lateral hypothalamus (LH) in the same behavioral paradigm.
机译:DA受体(DA-R)已被确定为了解奖励相关行为处理的潜在目标。多巴胺3受体(D3-R)在中脑多巴胺能回路中表达,表明D3-R处的DA信号可能对抑制奖赏过程至关重要。为缺乏D3-R(D3-R-/-)和野生型(D3-R + / +)的小鼠提供3个月的标准啮齿动物食物或优选的高脂(HF)饮食。接触3个月后,处死小鼠,测量体重,肥胖,食物摄入,血浆胰岛素和瘦素,并评估代谢指标。在优选的HF饮食中,D3-R-/-变得肥胖,但缺乏明显的食物摄入表型。因此,据推测,D3-R处的信号传导使动物能够整合有关周围能量可用性的信号并适当地调整食物摄入量。巯基乙酸盐(MA),2-脱氧-d-葡萄糖(2-DG)和胰岛素在增加D3-R-/-小鼠的食物摄入方面无效,但是外周葡萄糖和脂肪酸对药物的反应正常升高。相反,突变小鼠对瘦素和胰岛淀粉样蛋白的厌食作用反应过度。为了进一步表征奖励相关行为,D3-R-/-和+ / +小鼠可以接触到浓度越来越高的乙醇。乙醇摄入量很重要,因为已经假设多巴胺能回路可以介导消耗量,并且是具有心理药理学性质的热量来源。基于基因型,D3-R-/-小鼠的消耗量增加。为了评估假设的D3-R对食物摄入的抑制作用,我们在不同剥夺水平的三种不同喂养方案中,向有食物或高脂饮食的大鼠施用了D3-R激动剂(7-OH-DPAT)。在最后一组实验中,可以进食食物或HF饮食的动物受到食物限制。在测试当天,对接受预期饮食或违反预期饮食(正负预期)的动物给予7-OH-DPAT。 7-OH-DPAT减少了正对比剂的摄入量,而在其他条件下却没有减少摄入量。为了表征可能会影响这种作用的D3-Rs的中心种群,将7-OH-DPAT以相同的行为模式直接施用于伏伏核(NAcc)或下丘脑外侧(LH)。

著录项

  • 作者单位

    University of Cincinnati.;

  • 授予单位 University of Cincinnati.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 264 p.
  • 总页数 264
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;
  • 关键词

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