Deconstructing craving: dissociable cortical control of cue reactivity in nicotine addiction.
Deconstructing craving: dissociable cortical control of cue reactivity in nicotine addiction.
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DOI：
10.1016/j.biopsych.2011.01.023
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发表时间：
2011-06-01
影响因子：
10.6
通讯作者：
Hiroi, Noboru
中科院分区：
文献类型：
--
作者：
Scott, Daniel;Hiroi, Noboru
线索反应，与成瘾物质相关的线索诱导寻求和戒断的能力，是成瘾的主要原因。尽管人类成像研究表明，与香烟相关的线索同时激活脑岛和眶额皮质并唤起渴望，但这些活动如何在功能上对线索反应的不同元素做出贡献仍不清楚。此外，目前还不清楚这些皮层区域的同时激活是否反映了协调的功能连接或并行处理。我们选择性地用兴奋性毒素鹅膏蕈氨酸损伤小鼠的前额叶或眶额叶皮质，并在位置条件化范式中分别检查它们对尼古丁相关线索的接近（n = 6-13/组）和对戒断相关线索的回避（n = 5-12/组）。我们还测试了这两种皮质结构在接近食物相关线索（n = 6-7/组）和回避LiCl相关线索（n = 6-7/组）中的作用。我们的数据显示了双重分离，其中岛叶和眶额皮质的兴奋性毒性损伤分别选择性地扰乱尼古丁诱导的线索接近和戒断诱导的线索回避。这些影响并没有完全概括到接近食物相关的线索或避免氯化锂相关的线索。我们的数据提供的功能证据表明，在成瘾中看到的线索反应包括独特的神经解剖学分离的元素，并建议这两个皮层区域在响应吸烟相关的线索的同时激活并不一定表明功能连接。
Cue reactivity, the ability of cues associated with addictive substances to induce seeking and withdrawal, is a major contributor to addiction. Although human imaging studies show that cigarette-associated cues simultaneously activate the insula and the orbitofrontal cortex and evoke craving, how these activities functionally contribute to distinct elements of cue reactivity remains unclear. Moreover, it remains unclear whether the simultaneous activation of these cortical regions reflects coordinated functional connectivity or parallel processing. We selectively lesioned the insula or orbitofrontal cortex with the excitotoxin ibotenic acid in mice, and their approach to nicotine-associated cues (n = 6–13/group) and avoidance of withdrawal-associated cues (n = 5–12/group) were separately examined in place conditioning paradigms. We additionally tested the role of these two cortical structures in approach to food-associated cues (n = 6–7/group) and avoidance of LiCl-associated cues (n = 6–7/group). Our data show a double dissociation in which excitotoxic lesions of the insula and orbitofrontal cortex selectively disrupted nicotine-induced cue approach and withdrawal-induced cue avoidance, respectively. These effects were not entirely generalized to approach to food-associated cues or avoidance of LiCl-associated cues. Our data provide functional evidence that cue reactivity seen in addiction includes unique neuroanatomically dissociable elements and suggest that the simultaneous activation of these two cortical regions in response to smoking-related cues does not necessarily indicate functional connectivity.
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