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多巴胺 D3 受体突变小鼠对蔗糖的味觉敏感性降低。

Decreased taste sensitivity to sucrose in dopamine D3 receptor mutant mice.

机构信息

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology College, Xi'an Jiaotong University, 98 Xi Wu Road, Xi'an, Shaanxi 710004, P.R. China.

Department of Physiology and Pathophysiology, Health Science Center, Xi'an Jiaotong University, 76 West Yan Ta Road, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Chem Senses. 2022 Jan 1;47. doi: 10.1093/chemse/bjac014.

DOI:10.1093/chemse/bjac014
PMID:35762652
Abstract

Dopamine plays a key role in food rewards and sweet-taste stimulation. We examined the basis for behavioral responses to sweet taste in dopamine D3 receptor-deficient (D3-/-) mice by determining whether the absence of D3 receptors affects the sensitivity to dilute sucrose solutions. In experiment 1, we measured the intensity generalization threshold of conditioned taste aversion (CTA) to a 0.2 M sucrose solution. Results showed that the generalization thresholds were 0.025-0.05 M in D3-/- mice and 0.0025-0.005 M in wild-type (WT) mice. In experiment 2, we found that D3-/- and WT mice had similar capabilities to form and extinguish CTAs. Since the intensity generalization threshold is mainly due to a combination of sweet-taste sensitivity and the robust nature of CTA formation, the results showed that taste sensitivity to sucrose in D3-/- mice was lower than that in WT mice. In experiment 3, to test whether the peripheral sensory signaling may also be affected by the disruption of the dopamine D3 receptors, the mRNA expression levels of sweet-taste-related proteins in taste buds of D3-/- mice were determined. The T1R1 and BDNF mRNA expression levels in D3-/- mice were higher than the controls, whereas T1R2, T1R3, α-gustducin, and TRPM5 mRNA were similar. These findings suggest that disruption of dopamine D3 receptor-mediated signaling decreases the sweet-taste sensitivity and alters the mRNA expression levels of some taste-related molecules.

摘要

多巴胺在食物奖励和甜味刺激中起着关键作用。我们通过确定多巴胺 D3 受体缺失(D3-/-)小鼠对甜味的行为反应的基础,研究了 D3 受体缺失是否影响对稀释蔗糖溶液的敏感性。在实验 1 中,我们测量了条件味觉厌恶(CTA)对 0.2 M 蔗糖溶液的强度概括阈值。结果表明,D3-/- 小鼠的概括阈值为 0.025-0.05 M,而野生型(WT)小鼠的概括阈值为 0.0025-0.005 M。在实验 2 中,我们发现 D3-/- 和 WT 小鼠具有形成和消除 CTA 的相似能力。由于强度概括阈值主要是由于甜味敏感性和 CTA 形成的稳健性的结合,因此结果表明 D3-/- 小鼠对蔗糖的味觉敏感性低于 WT 小鼠。在实验 3 中,为了测试多巴胺 D3 受体的破坏是否也会影响外周感觉信号,我们测定了 D3-/- 小鼠味蕾中甜味相关蛋白的 mRNA 表达水平。D3-/- 小鼠的 T1R1 和 BDNF mRNA 表达水平高于对照,而 T1R2、T1R3、α- gustducin 和 TRPM5 mRNA 则相似。这些发现表明,多巴胺 D3 受体介导的信号转导的破坏降低了甜味敏感性,并改变了一些味觉相关分子的 mRNA 表达水平。

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