Effects of disconnection of amygdala dopamine and nucleus accumbens N-methyl-d-aspartate receptors on ethanol-seeking behavior in mice.
Effects of disconnection of amygdala dopamine and nucleus accumbens N-methyl-d-aspartate receptors on ethanol-seeking behavior in mice.
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DOI：
10.1111/j.1460-9568.2009.07044.x
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Cunningham CL
中科院分区：
文献类型：
--
作者：
Gremel CM;Cunningham CL
人们对利用小鼠中可能的遗传操作来研究调节控制药物寻求行为的关联过程的功能性神经机制有着浓厚的兴趣。然而，目前尚不清楚是否颅内技术，如断开程序通常用于大鼠检查牵连区域之间的串行连接可以成功地应用于小鼠。我们先前已经证明，小鼠乙醇寻求行为的表达依赖于杏仁核（Amy）多巴胺和杏仁核（Acb）NMDA受体的激活。在这里，我们使用的神经药理学断开程序，以调查是否多巴胺激活艾米直接导致增加Acb谷氨酸释放和NMDA受体的结合调节乙醇寻求行为的表达。在测试乙醇诱导的条件性位置偏爱（CPP）的表达之前，立即给予小鼠氟哌噻吨的Amy输注和AP-5的同侧或对侧Acb输注。虽然同侧和对侧操作都减少了乙醇CPP的表达，但在单独的实验中，我们证明了单侧Acb AP-5输注，而不是Amy Flu，足以破坏偏好。单侧AP-5对Acb的显著阻断的发现排除了关于Amy-Acb神经解剖学连接在这种乙醇寻求行为模型中的独特作用的任何结论。此外，目前的结果表明，潜在的局限性，从大鼠转移到小鼠的技术，以研究潜在的动机行为的神经区域之间的串行相互作用。然而，这些研究结果提供了证据表明，Acb NMDA受体在乙醇条件行为的表达中起着重要作用。
There is a strong interest in harnessing the genetic manipulations possible in mice to investigate functional neural mechanisms modulating associative processes that control drug-seeking behavior. However, it is unknown whether intra-cranial techniques such as the disconnection procedure commonly used in rats to examine serial connectivity between implicated areas can be successfully applied to mice. We have previously demonstrated that expression of ethanol-seeking behavior in mice is dependent upon amygdala (Amy) dopamine- and nucleus accumbens (Acb) NMDA- receptor activation. Here, we use a neuropharmacological disconnection procedure to investigate whether dopamine activation of Amy directly leading to increases in Acb glutamate release and binding of NMDA receptors modulates expression of ethanol-seeking behavior. Immediately before testing the expression of an ethanol-induced conditioned place preference (CPP), mice were given an Amy infusion of flupenthixol and either an ipsi- or contra-lateral Acb infusion of AP-5. While both ipsi- and contra-lateral manipulations reduced expression of ethanol CPP, in a separate experiment we demonstrate that a unilateral Acb AP-5 infusion, but not Amy Flu, is sufficient to disrupt preference. The finding of significant blockade by a unilateral AP-5 into Acb precludes any conclusions about a unique role for the Amy-Acb neuroanatomical connection in this model of ethanol-seeking behavior. Further, the current results suggest potential limitations in transferring techniques from rats to mice in order to study serial interactions between neural areas underlying motivated behaviors. Nevertheless, these findings provide evidence showing that Acb NMDA receptors play an important role in expression of ethanol-conditioned behavior.
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