Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats
Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats
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DOI：
10.1007/s00213-002-1196-x
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
See, RE
中科院分区：
文献类型：
--
作者：
McLaughlin, J;See, RE
理由. .先前与可卡因配对的环境刺激可以诱发人类的渴望，并在实验动物中恢复已消失的可卡因寻求行为。先前的证据表明杏仁核和前额叶皮层（PFC）可能是条件提示复发的基底。目标. .为了直接测试PFC在复发模型中的作用，本研究检测了三个内侧PFC区域，前扣带（ace），前边缘皮层（PL）和边缘下皮层（IL）的可逆失活对条件提示的可卡因寻求行为恢复表达的影响。我们还测试了基底外侧杏仁核（BLA）和顶叶皮质的受累程度，顶叶皮质紧背于BLA，感觉皮质区1 -桶区（S1BF）。方法. .在每天3小时的疗程中，大鼠按下杠杆进行静脉注射可卡因，并伴有浅色（LT）呈现。在没有LT的情况下，杠杆按压消失后，在没有可卡因的情况下，在LT的反应条件下，测量了消失的杠杆按压的恢复。对于局部可逆失活，在恢复测试之前，双侧注入河豚毒素（TTX） （5ng /0.5 ml /侧）或载体。结果. .BLA、acei或PL的TTX失活损害了LT呈现对可卡因配对刺激恢复已熄灭的杠杆按压的能力。相反，IL或S1BF的失活对条件提示恢复没有影响。此外，在任何被测试的大脑区域，TTX对一般运动活动都没有影响。结论. .这些结果支持了后内侧PFC和BLA在可卡因相关刺激引起的药物寻求行为的回路中的作用。在最近使用药物启动和应激诱导恢复模型的研究背景下，我们认为后内侧PFC可能在药物寻求行为恢复的神经回路中起着共同的作用。
Rationale.. Environmental stimuli previously paired with cocaine can induce craving in humans and reinstate extinguished cocaine-seeking behavior in laboratory animals. Previous evidence has implicated the amygdala and the prefrontal cortex (PFC) as possible substrates for conditioned-cued relapse. Objectives.. In order to test directly the role of the PFC in a model of relapse, the present study examined the effects of reversible inactivation of three medial PFC areas, the anterior cingulate (ACing), the prelimbic cortex (PL), and the infralimbic cortex (IL), on the expression of conditioned-cued reinstatement of extinguished cocaine-seeking behavior. We also tested the involvement of the basolateral amygdala (BLA) and the parietal cortex immediately dorsal to the BLA, sensory cortex area 1 - barrel field (S1BF). Methods.. During daily 3-h sessions, rats pressed a lever for IV cocaine infusions that were paired with a light-tone (LT) presentation. Following extinction of lever pressing in the absence of the LT, reinstatement of extinguished lever pressing was measured during response-contingent presentations of the LT in the absence of cocaine. For localized reversible inactivation, tetrodotoxin (TTX) (5 ng/0.5 mul/side) or vehicle was bilaterally infused just prior to reinstatement testing. Results.. TTX inactivation of the BLA, ACing, or PL impaired the ability of LT presentations to reinstate extinguished lever pressing for cocaine-paired stimuli. In contrast, inactivation of the IL or the S1BF had no effect on conditioned-cued reinstatement. Furthermore, there was no effect of TTX in any of the tested brain regions on general locomotor activity. Conclusions.. These results support a role for the dorsomedial PFC and the BLA in the circuitry that mediates drug-seeking behavior elicited by cocaine-associated stimuli. Placed within the context of recent studies using drug-primed and stress-induced reinstatement models, we suggest that the dorsomedial PFC may serve as a common link in the neural circuitry underlying reinstatement of drug-seeking behavior.