Renewal of extinguished cocaine-seeking
Renewal of extinguished cocaine-seeking
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DOI：
10.1016/j.neuroscience.2007.11.018
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发表时间：
2008-02-06
期刊：
影响因子：
3.3
通讯作者：
Mcnally, G. P.
中科院分区：
文献类型：
--
作者：
Hamlin, A. S.;Clemens, K. J.;Mcnally, G. P.
训练大鼠在独特的环境（环境 A）中自我施用可卡因。然后在原始训练环境、环境 A（ABA 组）、环境 B（ABB 组）或无测试（ABO 组）中进行可卡因寻求测试之前，在第二环境（环境 B）中熄灭它们。 ABA 组表现出与基底外侧杏仁核、外侧下丘脑和下边缘前额皮质中 c-Fos 诱导相关的已熄灭的可卡因寻求的更新。 ABA 和 ABB 组在边缘前额皮质、伏核（核、壳、头极）、纹状体、外侧杏仁核、下丘脑周围和腹侧被盖区显示出与测试相关的 c-Fos 诱导。双重免疫荧光显示，更新相关的 c-Fos 在食欲素阴性的下丘脑外侧神经元中表达，而测试相关的 c-Fos 在食欲素阳性的角周神经元中表达。用霍乱毒素从下丘脑外侧逆行追踪发现，基底外侧杏仁核和边缘下前额皮质中仅存在稀疏的双标记神经元，这表明这些区域有助于可卡因寻求的更新，而与它们对下丘脑外侧的投射无关。从腹侧被盖区逆行追踪表明，下丘脑对可卡因寻求的贡献同样独立于对中脑的投射。这些结果表明，可卡因寻求的更新关键取决于基底外侧杏仁核、外侧下丘脑和边缘下前额皮质。虽然基底外侧杏仁核和外侧下丘脑的贡献对于已熄灭的可卡因、酒精和蔗糖的寻求的更新可能是常见的，但边缘下前额叶皮层的贡献似乎对于可卡因寻求的更新是独特的，并且可能反映了可卡因复发的习惯性本质。 (c) 2007 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Rats were trained to self-administer cocaine in a distinctive context (context A). They were then extinguished in a second context (context B) prior to test for cocaine-seeking in the original training context, context A (group ABA), context B (group ABB) or no test (group ABO). Group ABA showed renewal of extinguished cocaine-seeking associated with c-Fos induction in basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area. Double immunofluorescence revealed that renewal-associated c-Fos was expressed in orexin-negative lateral hypothalamic neurons whereas test-associated c-Fos was expressed in orexin-positive perifornical hypothalamic neurons. Retrograde tracing from lateral hypothalamus with cholera toxin revealed only sparse dual-labeled neurons in basolateral amygdala and infralimbic prefrontal cortex, suggesting that these regions contribute to renewal of cocaine-seeking independently of their projections to lateral hypothalamus. Retrograde tracing from the ventral tegmental area suggested that hypothalamic contributions to cocaine-seeking are likewise independent of projections to the midbrain. These results suggest that renewal of cocaine-seeking depends critically on basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Whereas basolateral amygdala and lateral hypothalamus contributions may be common to renewal of extinguished cocaine-, alcohol-, and sucrose-seeking, infralimbic prefrontal cortex contributions appear unique to renewal of cocaine-seeking and may reflect the habitual nature of relapse to cocaine. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.