Chronic Mild Stress Increases Alcohol Intake in Mice With Low Dopamine D2 Receptor Levels
Chronic Mild Stress Increases Alcohol Intake in Mice With Low Dopamine D2 Receptor Levels
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DOI：
10.1037/a0030750
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发表时间：
2013-02-01
影响因子：
1.9
通讯作者：
Volkow, Nora D.
中科院分区：
文献类型：
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作者：
Delis, Foteini;Thanos, Panayotis K.;Volkow, Nora D.
酒精使用障碍源于环境和遗传因素之间复杂的相互作用。压力和多巴胺D2受体水平（DRD 2）已被证明在酒精中毒中发挥核心作用。为了更好地理解DRD 2与乙醇摄入行为中的应激之间的相互作用，我们使Drd 2野生型（+/+）、杂合型（+/-）和敲除型（-/-）小鼠经历4周的慢性轻度应激（CMS），并在CMS第2-4周期间进行乙醇双瓶选择。在实验之前和实验结束时，在强迫游泳和旷场测试中测试动物。我们测量了乙醇的摄入量和偏好，不动力游泳测试，并在开放领域的活动。我们发现，在没有CMS的情况下，与Drd 2 +/+相比，Drd 2 +/-和Drd 2-/-小鼠的乙醇摄入量和偏好较低。暴露于CMS降低了Drd 2 +/+小鼠的乙醇摄入量和偏好，并增加了Drd 2 +/-和Drd 2-/-小鼠的乙醇摄入量和偏好。在基线时，Drd 2 +/-和Drd 2-/-小鼠在旷场中的活动显著低于Drd 2 +/+，而在强迫游泳试验中未观察到基因型差异。在强迫游泳试验中，暴露于CMS增加了Drd 2 +/-小鼠的不动性，但在Drd 2 +/+或Drd 2-/-小鼠中没有，乙醇摄入逆转了这一行为。未观察到旷场试验测量值发生变化。这些发现表明，在压力环境中，低DRD 2水平与乙醇摄入量和偏好增加有关，在这种情况下，增加乙醇摄入量可以作为缓解负面情绪的策略。
Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood.