Short Jennifer Lynn, Ledent Catherine, Drago John, Lawrence Andrew John
Department of Pharmacology, Faculty of Medicine, Monash University, Clayton, VIC, Australia.
Neuropsychopharmacology. 2006 Mar;31(3):525-34. doi: 10.1038/sj.npp.1300852.
Here we report the development of D1A2A receptor knockout mice to investigate whether interactions between dopamine D1 and adenosine A2A receptors participate in reward-related behavior. The combined deletion of D1 and A2A receptors resulted in mice with decreased weight and appetitive processes, reduced rearing and exploratory behaviors, increased anxiety, and a significantly poorer performance on the rotarod, compared to wild-type littermates. D1A2A receptor knockout mice shared phenotypic similarities with mice deficient in D1 receptors, while also paralleling behavioral deficits seen in A2A receptor knockout mice, indicating individual components of the behavioral phenotype of the D1A2A receptor knockout attributable to the loss of both receptors. In contrast, ethanol and saccharin preference in D1A2A receptor knockout mice were distinctly different from that observed in derivative D1 or A2A receptor-deficient mice. Compared to wild types, preference and consumption of ethanol were decreased in D1A2A receptor knockout mice, the reduction in ethanol consumption greater even than that seen in D1 receptor-deficient mice. Preference and consumption of saccharin were also reduced in D1A2A receptor knockout mice, whereas saccharin preference was similar in wild-type, D1, and A2A receptor knockout mice. These data suggest an interaction of D1 and A2A receptors in the reinforcement processes underlying the intake of rewarding substances, whereby the A2A receptor seems involved in goal-directed behavior and the motor functions underlying the expression of such behaviors, and the D1 receptor is confirmed as essential in mediating motivational processes related to the repeated intake of novel substances and drugs.
在此，我们报告D1A2A受体敲除小鼠的培育情况，以研究多巴胺D1受体与腺苷A2A受体之间的相互作用是否参与与奖赏相关的行为。与野生型同窝小鼠相比，D1和A2A受体的联合缺失导致小鼠体重减轻、食欲减退、竖毛和探索行为减少、焦虑增加，并且在转棒试验中的表现明显更差。D1A2A受体敲除小鼠与D1受体缺陷小鼠具有相似的表型特征，同时也与A2A受体敲除小鼠出现的行为缺陷相似，这表明D1A2A受体敲除小鼠行为表型的各个组成部分可归因于两种受体的缺失。相比之下，D1A2A受体敲除小鼠对乙醇和糖精的偏好与衍生的D1或A2A受体缺陷小鼠明显不同。与野生型相比，D1A2A受体敲除小鼠对乙醇的偏好和摄入量降低，乙醇摄入量的减少甚至比D1受体缺陷小鼠更明显。D1A2A受体敲除小鼠对糖精的偏好和摄入量也降低，而野生型、D1和A2A受体敲除小鼠对糖精的偏好相似。这些数据表明D1和A2A受体在奖赏性物质摄入所涉及的强化过程中存在相互作用，其中A2A受体似乎参与目标导向行为以及此类行为表达所涉及的运动功能，而D1受体被证实对于介导与反复摄入新物质和药物相关的动机过程至关重要。
