Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice
Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice
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DOI：
10.1016/j.neuropharm.2005.12.005
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发表时间：
2006-06-01
影响因子：
4.7
通讯作者：
Hungund, Basalingappa L.
中科院分区：
文献类型：
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作者：
Basavarajappa, Balapal S.;Yalamanchili, Ratnakumar;Hungund, Basalingappa L.
先前的研究表明，缺乏大麻素(CB 1)受体基因的小鼠消耗的乙醇水平明显减少。缺乏脂肪酸氨基水解酶(FAAH)的小鼠降解氨基甲酰胺(AEA)的能力严重受损，因此是一种独特的动物模型，可以在体内研究AEA对饮酒行为的作用。在目前的研究中，对FAAH(-/-)小鼠进行了乙醇、糖精或奎宁的消耗和偏好测试。以乙醇诱导的体温降低和睡眠时间为指标评价小鼠对乙醇急性反应的敏感性。只有雌性FAAH(-/-)小鼠的乙醇摄入量和偏好增加。糖精或奎宁的摄入量或偏好在不同的基因型间没有显著差异。雌性FAAH(-/-)小鼠对急性乙醇的降温和镇静/催眠作用不太敏感。雄性和雌性FAAH(-/-)小鼠对外源性AEA均具有超敏反应。在自愿饮酒后，雄性FAAH(+/+)、FAAH(-/-)和雌性FAAH(+/+)小鼠的CB1受体水平和功能下调，而雌性FAAH(-/-)小鼠没有下调。我们的结果表明，在雄性小鼠中没有这种影响表明了一种性别相关的机制，这种机制是FAAH功能的次要(或调节)机制。因此，这些数据表明FAAH可能与酒精摄取和敏感性间接相关，中枢内源性大麻能介导的通路可能调节酒精的消耗。(C)2005爱思唯尔有限公司。保留所有权利。
Previous studies have shown that mice lacking cannabinoid (CB 1) receptor gene consume markedly reduced levels of ethanol. Mice lacking the enzyme fatty acid amidohydrolase (FAAH) are severely impaired in their ability to degrade anandamide (AEA) and therefore represent a unique animal model in which to examine the function of AEA in vivo on ethanol-drinking behavior. In the current study, FAAH(-/-) mice were tested for ethanol, saccharin or quinine consumption and preference. Ethanol-induced hypothermia, and sleep time were used to evaluate the sensitivity to acute effects of ethanol. Ethanol intake and preference were increased only in female FAAH(-/-) mice. No significant difference in saccharin or quinine consumption or preference was observed between genotypes. Female FAAH(-/-) mice were less sensitive to the hypothermic and sedative/hypnotic effects of acute ethanol. Supersensitivity to exogenous AEA was noted in both male and female FAAH(-/-) mice. Following voluntary ethanol consumption, CB 1 receptor levels and function were down-regulated in male FAAH(+/+), FAAH(-/-), and female FAAH(+/+) mice but not in female FAAH(-/-) mice. Our results suggest that absence of an effect in male mice indicates a sex-linked mechanism that is secondary (or modulatory) to FAAH function. Thus, the data suggest that FAAH may be indirectly related to ethanol intake and sensitivity and central endocannabinoidergic-mediated pathways may regulate ethanol consumption. (c) 2005 Elsevier Ltd. All rights reserved.