Altered Fos expression in neural pathways underlying cue-elicited drug seeking in the rat
Altered Fos expression in neural pathways underlying cue-elicited drug seeking in the rat
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DOI：
10.1111/j.1460-9568.2005.03974.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Marshall, JF
中科院分区：
文献类型：
--
作者：
Miller, CA;Marshall, JF
与环境线索配对的条件反射处理建立了对该环境的条件位置偏好。表达这种偏好后，与药物未配对对照组相比，大鼠在前边缘皮质（PrL）、基底外侧杏仁核复合体（BLC）和杏仁核核心（NAcc）中显示出升高的立即早期基因（例如c-fos）水平。PrL和BLC是串联连接的，都投射到NAcc。这些联系与早期基因的发现一起表明，这些区域作为一个回路相互作用，有助于线索引发的药物寻找。为了研究这个电路，我们离子电渗荧光金（FG）到一个大脑区域，并评估共定位FG与位置偏好诱导的Fos在其他。在PrL或NAcc中FG离子电渗后，在药物配对的动物中发现更多的Fos和FG双标记的BLC细胞。在BLC或NAcc中FG离子电渗后，未发现PrL Fos/FG细胞的绝对数量存在差异。这种共定位模式表明，暴露于可卡因相关线索会导致BLC向PrL和NAcc的传出神经更大程度地激活，而向NAcc和BLC输出的PrL对IEG表达不受影响。这些结果补充了最近的研究结果，表明衰减的PrL输出在位置偏好表达。我们的研究结果支持这样的观点，即BLC，而不是PrL，提供了显着的兴奋性驱动的NAcc在线索引起的药物寻求。
Cocaine treatment paired with environmental cues establishes a conditioned place preference for that environment. Following expression of this preference, rats show elevated levels of immediate early genes (e.g. c-fos) in the prelimbic cortex (PrL), basolateral amygdala complex (BLC) and nucleus accumbens core (NAcc) compared to drug-unpaired controls. The PrL and BLC are reciprocally connected and both project to the NAcc. Together with the immediate early gene findings, these connections suggest the regions interact as a circuit contributing to cue-elicited drug seeking. To study this circuit, we iontophoresed Fluorogold (FG) into one brain region and assessed colocalization of FG with place preference-induced Fos in the others. Following FG iontophoresis in either the PrL or NAcc, more BLC cells double-labelled for Fos and FG were found in drug-paired than unpaired animals. Following FG iontophoresis in either the BLC or NAcc, no differences were found in the absolute number of PrL Fos/FG cells. This pattern of colocalization suggests that exposure to cocaine-associated cues leads to greater activation of the BLC's efferents to both the PrL and NAcc, while PrL output to the NAcc and BLC is unaffected in IEG expression. These results complement recent findings that suggested attenuated PrL output during place preference expression. Our findings support the view that the BLC, rather than the PrL, provides significant excitatory driving to the NAcc during cue-elicited drug seeking.