Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior
Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior
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DOI：
10.1016/s0014-2999(98)00414-2
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发表时间：
1998-07-24
影响因子：
5
通讯作者：
O'Dowd, BF
中科院分区：
文献类型：
--
作者：
El-Ghundi, M;George, SR;O'Dowd, BF
在多巴胺D-1受体（D-1 -/-）基因缺陷的小鼠中，研究了多巴胺D-1受体亚型在寻求酒精行为中的作用。在双管自由选择有限（1-5 h）和连续（24 h）模式下，小鼠暴露于水和增加浓度的乙醇（3%，6%和12% w/v）。与杂合子（D-1 +/-）和野生型（D-1 +/+）对照相比，D-1 -/-小鼠的自愿乙醇消耗和对水的偏好明显减少，而总体液体消耗是相当的。当给D-1 -/-小鼠提供一个含酒精的饮用管作为其唯一的液体来源24小时时，D-1 -/-小鼠继续比D-1 +/+和D-1 +/-小鼠喝更少的酒精。用舒必利阻断多巴胺D-2受体，使D-1 +/+小鼠的酒精摄入量和偏好减少，D-1 -/-小鼠的残余酒精摄入量减少，但效果显著。用SCH-23390阻断多巴胺D-1受体非常有效地将D-1 +/+和D-1 +/-小鼠的酒精摄入量减少到未治疗的D-1 -/-小鼠的水平。这些发现表明多巴胺D-1和D-2受体机制参与了小鼠的酒精寻求行为；然而，这些暗示D-1受体在饮酒动机中起着更重要的作用。(C) 1998 Elsevier Science B.V.版权所有
The role of the dopamine D-1 receptor subtype in alcohol-seeking behaviors was studied in mice genetically deficient in dopamine D-1 receptors (D-1 -/-). In two-tube free choice limited (1-5 h) and continuous (24 h) access paradigms, mice were exposed to water and increasing concentrations of ethanol (3%, 6% and 12% w/v). Voluntary ethanol consumption and preference over water were markedly reduced in D-1 -/- mice as compared to heterozygous (D-1 +/-) and wild-type (D-1 +/+) controls, whereas overall fluid consumption was comparable. When offered a single drinking tube containing alcohol as their only source of fluid for 24 h, D-1 -/- mice continued to drink significantly less alcohol than D-1 +/+ and D-1 +/- mice. Dopamine D-2 receptor blockade with sulpiride caused a small but significant reduction in alcohol intake and preference in D-1 +/+ mice and attenuated residual alcohol drinking in D-1 -/- mice. Dopamine D-1 receptor blockade with SCH-23390 very effectively reduced alcohol intake in D-1 +/+ and D-1 +/- mice to the level seen in untreated D-1 -/- mice. These findings suggest involvement of both dopamine D-1 and D-2 receptor mechanisms in alcohol-seeking behavior in mice; however, these implicate D-1 receptors as having a more important role in the motivation for alcohol consumption. (C) 1998 Elsevier Science B.V. All rights reserved.