Homer2 gene deletion in mice produces a phenotype similar to chronic cocaine treated rats
Homer2 gene deletion in mice produces a phenotype similar to chronic cocaine treated rats
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DOI：
10.1007/bf03033313
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Worley, P
中科院分区：
文献类型：
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作者：
Kalivas, PW;Szumlinski, KK;Worley, P
可卡因成瘾是由于药理学、环境条件以及遗传脆弱性共同作用而引起的大脑功能变化。其中一个变化是丘脑核中Homer蛋白的减少。在这份报告中，我们总结了Homer2基因缺失对小鼠行为和神经化学的影响，并将其与慢性可卡因治疗对大鼠的影响进行了比较。结果表明，Homer2 KO小鼠表现出对可卡因的增强的运动刺激和条件性位置偏爱反应。Homer2缺失还导致小鼠在延髓核中显示出基础细胞外谷氨酸盐减少，并且响应于可卡因注射而使细胞外谷氨酸盐敏化增加。与谷氨酸相反，Homer2 KO小鼠在可卡因激发注射后表现出细胞外多巴胺的正常增加。Homer 2基因缺失和慢性可卡因给药对可卡因的行为和神经元化学反应的影响之间的平行关系支持Homer蛋白和谷氨酸传递参与重复可卡因产生的行为敏化。
Addiction to cocaine results from changes in brain function arising from a combination of pharmacology, environmental circumstances, as well as genetic vulnerability. One change is a reduction in Homer protein in the nucleus accumbens. In this report we summarize the behavioral and neurochemical effects of Homer2 gene deletion in mice and compare this with the effects of chronic cocaine treatment in rats. It was shown that Homer2 KO mice demonstrate enhanced locomotor stimulant and conditioned place preference responses to cocaine. Homer2 deletion also caused mice to show reduced basal extracellular glutamate in the nucleus accumbens and a sensitized increase in extracellular glutamate in response to a cocaine injection. In contrast to glutamate, Homer2 KO mice showed a normal increase in extracellular dopamine following a cocaine challenge injection. The parallel between the effect of Homer2 gene deletion and chronic cocaine administration on behavioral and glutamatergic neurochemical responses to cocaine supports involvement of Homer proteins and glutamate transmission in the sensitization of behavior produced by repeated cocaine.