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宫内发育受限增加冲动行为,并与雌性大鼠中前额皮质内侧和眶额皮质多巴胺传递的改变有关。

Intrauterine growth restriction increases impulsive behavior and is associated with altered dopamine transmission in both medial prefrontal and orbitofrontal cortex in female rats.

机构信息

Programa de Pós Graduação em Bioquímica, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Programa de Pós Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Physiol Behav. 2019 May 15;204:336-346. doi: 10.1016/j.physbeh.2019.03.010. Epub 2019 Mar 14.

DOI:10.1016/j.physbeh.2019.03.010
PMID:30880239
Abstract

Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR. From day 10 of pregnancy and until birth, Sprague-Dawley dams received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, all pups were adopted by Adlib mothers, generating the groups Adlib/Adlib (control) and FR/Adlib (intrauterine growth-restricted). Adult impulsive behavior was evaluated using a Tolerance to Delay of Reward Task. In vivo dopamine responses to sweet food intake were measured by voltammetry, and D1, D2 and DAT levels were accessed by Western Blot. Animals from FR group showed a pronounced aversion to delayed rewards. DA response to sweet food was found to be blunted in the mPFC of FR animals, whereas in the OFC, the DA levels appear to be unaffected by reward consumption. Moreover, FR animals presented reduced D1 receptors in the OFC and a later increase in the mPFC D2 levels. These findings suggest that IUGR female rats are more impulsive and that the associated mechanism involves changes in the dopamine signaling in both the mPFC and OFC.

摘要

最近的研究表明,冲动性在改变的饮食行为和与宫内生长受限(IUGR)相关的肥胖风险增加中起作用。人们认为,前额叶区域的多巴胺传递变化导致了这些不良后果。在这里,我们研究了对延迟奖励的冲动行为,并评估了暴露于 IUGR 的雌性成年大鼠的内侧前额叶(mPFC)和眶额皮层(OFC)中的多巴胺水平及其受体。从怀孕的第 10 天到出生,Sprague-Dawley 母鼠接受了自由饮食(Adlib)或 50%食物限制(FR)饮食。出生时,所有幼崽都被 Adlib 母亲收养,产生了 Adlib/Adlib(对照)和 FR/Adlib(宫内生长受限)组。使用延迟奖励任务评估成年冲动行为。通过伏安法测量对甜食摄入的多巴胺反应,通过 Western Blot 测定 D1、D2 和 DAT 水平。来自 FR 组的动物对延迟奖励表现出明显的厌恶。发现 FR 动物的 mPFC 中对甜食的 DA 反应减弱,而在 OFC 中,DA 水平似乎不受奖励摄入的影响。此外,FR 动物在 OFC 中 D1 受体减少,而在 mPFC 中 D2 水平后期增加。这些发现表明,IUGR 雌性大鼠更冲动,相关机制涉及 mPFC 和 OFC 中多巴胺信号的变化。

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