Differential involvement of the prelimbic cortex and striatum in conditioned heroin and sucrose seeking following long‐term extinction
Differential involvement of the prelimbic cortex and striatum in conditioned heroin and sucrose seeking following long‐term extinction
复制标题
DOI：
10.1111/j.1460-9568.2005.04435.x
复制
发表时间：
2005-11
影响因子：
3.4
通讯作者：
E. Schmidt;P. Voorn;R. Binnekade;A. Schoffelmeer;T. J. de Vries
中科院分区：
文献类型：
--
作者：
E. Schmidt;P. Voorn;R. Binnekade;A. Schoffelmeer;T. J. de Vries
吸毒复发是由以前与滥用药物(CUES)相关的刺激触发的，涉及大脑系统控制对天然增强剂的动机行为。在这项研究中，我们旨在识别和比较控制条件海洛因或自然奖赏(蔗糖)寻求的皮质纹状体系统中的神经通路。为此，训练大鼠在相同的复合线索下自我给药海洛因或蔗糖。经过3周以上的消退训练戒断后，线索暴露使海洛因和蔗糖寻找行为恢复正常，但在大脑皮层和纹状体复合体中，神经元激活标志物Zif268的表达发生了明显甚至相反的变化。由于在线索诱导海洛因寻找时Zif268在前额叶的表达增强，而在蔗糖寻找时Zif268的表达不受影响，因此针对这一前额叶区域进行药物干预。在预备区注射GABA激动剂混合物可促进条件性海洛因寻找，但对条件性蔗糖寻找无影响。我们的发现表明，在海洛因长期戒断与寻求蔗糖的持续过程中，前脑区和纹状体扮演着不同的角色。
Relapse to drug taking is triggered by stimuli previously associated with consumption of drugs of misuse (cues) and involves brain systems controlling motivated behaviour towards natural reinforcers. In this study, we aimed to identify and compare neuronal pathways in corticostriatal systems that control conditioned heroin or natural reward (sucrose) seeking. To that end, rats were trained to self‐administer heroin or sucrose in association with an identical compound cue. After more than 3 weeks of abstinence during extinction training, cue exposure robustly reinstated heroin and sucrose seeking, but induced distinct and even opposing changes in the expression of the neuronal activation marker zif268 in the prelimbic cortex and striatal complex, respectively. Because in the prelimbic area zif268 expression was enhanced during cue‐induced heroin seeking but unaffected during sucrose seeking, a pharmacological intervention was aimed at this prefrontal region. Injection of a GABA agonist mixture within the prelimbic area enhanced conditioned heroin seeking, but had no effect on conditioned sucrose seeking. Our findings suggest a differential role of the prelimbic area and the striatum in the persistence of heroin vs. sucrose seeking following long‐term extinction.