Houchi H, Warnault V, Barbier E, Dubois C, Pierrefiche O, Ledent C, Daoust M, Naassila M
Equipe Région INSERM 24, Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie, Amiens, France.
Genes Brain Behav. 2008 Nov;7(8):887-98. doi: 10.1111/j.1601-183x.2008.00427.x.
We have shown previously that mice lacking the adenosine A2A receptor (A2AR) generated on a CD1 background self-administer more ethanol and exhibit hyposensitivity to acute ethanol. We aimed to investigate if the increased propensity of A2A(-/-) 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 A2A(-/-) mice produced on a CD1 background displayed a reduced ethanol-induced CPP and an increased sensitivity to the anxiolytic and locomotorstimulant 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 A2A(-/-) 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 A2AR agonist, 2-p-(2-carboxyethyl)-phenylethylamino-50-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J mice. In conclusion, A2AR 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.
我们之前已经表明，在CD1背景下产生的缺乏腺苷A2A受体（A2AR）的小鼠会自我摄入更多乙醇，并且对急性乙醇表现出低敏感性。我们旨在研究A2A基因敲除小鼠增加的乙醇摄入倾向是否与条件性位置偏爱（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有关，以及与乙醇运动效应致敏的发育改变有关。我们还测试了它们对乙醇抗焦虑作用的敏感性。我们的结果表明，在CD1背景下产生的A2A基因敲除小鼠表现出乙醇诱导的CPP降低，以及对乙醇抗焦虑和运动刺激作用的敏感性增加，但它们在乙醇诱导的CTA和运动致敏方面没有表现出改变。我们还在C57BL/6J背景下产生的A2A基因敲除小鼠中测试了乙醇诱导的CPP、乙醇消耗和乙醇的运动效应。我们的结果强调了遗传背景的重要性，因为在偏好酒精的C57BL/6J遗传背景下产生的基因敲除小鼠中未发现乙醇消耗和偏好、乙醇诱导的CPP和运动刺激作用的改变。最后，A2AR激动剂2 -对 -（2 -羧乙基）-苯乙胺基-5'-N -乙基羧酰胺基腺苷盐酸盐（CGS 21680）降低了C57BL/6J小鼠的乙醇消耗和偏好。总之，在CD1背景下产生的小鼠中A2AR缺乏导致高乙醇消耗，这与对乙醇运动刺激/抗焦虑作用的敏感性增加以及乙醇诱导的CPP降低有关。
