Belin David, Everitt Barry J
Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK.
Neuron. 2008 Feb 7;57(3):432-41. doi: 10.1016/j.neuron.2007.12.019.
A neuroanatomical principle of striatal organization has been established through which ventral domains, including the nucleus accumbens, exert control over dorsal striatal processes mediated by so-called "spiraling," striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the nucleus accumbens core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.
一种纹状体组织的神经解剖学原理已经确立，通过该原理，包括伏隔核在内的腹侧区域对由所谓的“螺旋式”纹状体 - 黑质 - 纹状体回路介导的背侧纹状体过程施加控制。我们通过使用一种纹状体内切断程序来研究该回路在控制可卡因寻求习惯中的功能意义，该程序结合了伏隔核核心的选择性单侧损伤以及向对侧背外侧纹状体注入多巴胺受体拮抗剂，从而双侧破坏纹状体 - 中脑 - 纹状体的连续连接。我们表明，这种切断选择性地降低了在可卡因强化二级程序下广泛训练的大鼠的药物寻求行为。这些数据因此确定了由多巴胺能传递介导的纹状体腹侧和背侧区域之间相互作用在可卡因寻求习惯的发展和表现的神经机制中的重要性，而可卡因寻求习惯是药物成瘾的一个关键特征。
