Altered prelimbic cortex output during cue-elicited drug seeking
Altered prelimbic cortex output during cue-elicited drug seeking
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DOI：
10.1523/jneurosci.1685-04.2004
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发表时间：
2004-08-04
影响因子：
5.3
通讯作者：
Marshall, JF
中科院分区：
文献类型：
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作者：
Miller, CA;Marshall, JF
可卡因治疗与环境线索相结合，建立了对该环境的条件性地点偏好(CPP)。在表达了这种偏好后，与未配对药物的对照组相比，大鼠在初级皮质(PRL)、基底外侧杏仁复合体(BLC)和伏核(NAcc)中的即刻早期基因(IEGs；例如c-fos)水平升高。这些发现，再加上这些区域之间已知的联系，表明它们起到了促进暗示引发渴望的回路的作用。为了研究这个回路在药物寻找过程中的功能，我们研究了每个区域特定神经元类别的Fos免疫反应。为了区分GABA能和非GABA能(主要是兴奋性投射)神经元的IEG激活，我们结合了Fos免疫组织化学和谷氨酸脱羧酶67(GAD(67))或钙/钙调蛋白依赖性蛋白激酶II(CaMKII)的免疫组织化学。在药物配对和药物未配对动物的BLC和NAcc中，我们观察到Fos免疫反应(IR)细胞的百分比也没有显著差异，GAD(67)-IR。我们也没有观察到BLC中Fos/CaMKII重叠程度的组间差异。然而，在PRL中，药物配对组的Fos/GAD(67)重叠程度显著高于未配对药物组。此外，在药物配对的动物中，整个PRL以及仅其第V层的Fos/CaMKII重叠显著低于对照组。这些发现表明，在可卡因配对动物的CPP表达过程中，PRL GABA能中间神经元优先激活，而PRL输出减弱，这可能是通过对V层锥体神经元的更大抑制。这些结果表明，在寻找可卡因的过程中，前额叶皮质细胞群的反应发生了变化。
Cocaine treatment paired with environmental cues establishes a conditioned place preference (CPP) for that environment. After expression of this preference, rats show elevated levels of immediate early genes (IEGs; e. g. c-fos) in the prelimbic cortex (PrL), basolateral amygdala complex (BLC), and nucleus accumbens core (NAcc) compared with drug-unpaired controls. These findings, together with the known connections between these regions, suggest that they function as a circuit contributing to cue-elicited craving. To investigate the function of this circuit during drug-seeking, we characterized Fos immunoreactivity of particular neuron classes in each region. To distinguish between IEG activation of GABAergic and non-GABAergic (principally, excitatory projection) neurons, we combined Fos immunohistochemistry with immunohistochemistry for glutamic acid decarboxylase 67 (GAD(67)) or calcium/calmodulin-dependent protein kinase II (CAMKII) proteins. Within the BLC and NAcc of drug-paired and drug-unpaired animals tested for CPP, we observed no significant differences in the percentage of Fos-immunoreactive (IR) cells that were alsoGAD(67)-IR. We also observed no group difference in the degree of Fos/CAMKII overlap in the BLC. However, in PrL, the degree of Fos/GAD(67) overlap in the drug-paired group was significantly higher than in the drug-unpaired group. Also, the Fos/CAMKII overlap in the entire PrL as well as just its layer V was significantly lower in the drug-paired animals compared with controls. These findings suggest that, during CPP expression in cocaine-paired animals, the PrL GABAergic interneurons are preferentially activated while PrL output is attenuated, perhaps through greater inhibition of layer V pyramidal neurons. These results suggest a shifting prefrontal cortex cell population response during cocaine-seeking.