Involvement of A2A receptors in anxiolytic, locomotor and motivational properties of ethanol in mice
Involvement of A2A receptors in anxiolytic, locomotor and motivational properties of ethanol in mice
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DOI：
10.1111/j.1601-183x.2008.00427.x
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发表时间：
2008-11-01
影响因子：
2.5
通讯作者：
Naassila, M.
中科院分区：
文献类型：
--
作者：
Houchi, H.;Warnault, V.;Naassila, M.
我们以前已经表明，缺乏腺苷A（2A）受体（A（2A）R）的小鼠产生的CD 1背景自我管理更多的乙醇和急性乙醇表现出低敏感性。我们的目的是研究A（2A）（-/-）小鼠消耗乙醇的倾向增加是否与条件性位置偏好（CPP）和条件性味觉厌恶（CTA）范式中乙醇动机特性的敏感性改变以及对乙醇运动效应的敏感性改变有关。我们还测试了它们对乙醇抗焦虑作用的敏感性。我们的研究结果表明，在CD 1背景下产生的A（2A）（-/-）小鼠显示出乙醇诱导的CPP降低，对乙醇的抗焦虑和运动刺激作用的敏感性增加，但它们没有显示出乙醇诱导的CTA和运动敏感性的改变。还在C57 BL/6 J背景下产生的A（2A）（-/-）小鼠中测试了乙醇诱导的CPP、乙醇消耗和乙醇的运动效应。我们的研究结果强调了遗传背景的重要性，因为在酒精消费和偏好，乙醇诱导的CPP和运动刺激的影响没有发现在基因敲除小鼠产生的酒精偏好C57 BL/6 J遗传背景的改变。最后，A（2A）R激动剂2-对-（2-羧乙基）-苯乙基氨基-5 '-N-乙基羧酰胺腺苷盐酸盐（CGS 21680）降低了C57 BL/6 J小鼠的乙醇消耗量和偏好。总之，在CD 1背景下产生的小鼠中A（2A）R缺乏导致高乙醇消耗，这与对乙醇的运动刺激/抗焦虑作用的敏感性增加和乙醇诱导的CPP降低有关。
We have shown previously that mice lacking the adenosine A(2A) receptor (A(2A)R) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol. We aimed to investigate if the increased propensity of A(2A)(-/-) mice to consume ethanol is associated with an altered sensitivity in the motivational properties of ethanol in the conditioned place preference (CPP) and conditioned taste aversion (CTA) paradigms and with an altered development of sensitization to the locomotor effects of ethanol. We also tested their sensitivity to the anxiolytic effects of ethanol. Our results show that A(2A)(-/-) mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotor-stimulant effects of ethanol, but they did not show alteration in ethanol-induced CTA and locomotor sensitization. Ethanol-induced CPP, ethanol consumption and the locomotor effects of ethanol were also tested in A(2A)(-/-) mice produced on a C57BL/6J background. Our results emphasized the importance of the genetic background because alteration in ethanol consumption and preference, ethanol-induced CPP and locomotor-stimulant effects were not found in knockout mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the A(2A)R agonist, 2-p-(2-carboxyethyl)-phenylethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice. In conclusion, A(2A)R deficiency in mice generated on a CD1 background leads to high ethanol consumption that is associated with an increased sensitivity to the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in ethanol-induced CPP.