Department of Psychology, University of North Carolina, Chapel Hill, NC 27599, USA.
Addict Biol. 2012 Mar;17(2):287-99. doi: 10.1111/j.1369-1600.2011.00325.x. Epub 2011 Apr 26.
The functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine-seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype 1 (mGluR1) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor populations to drug context-induced reinstatement of cocaine-seeking behavior. Rats were trained to lever press for un-signaled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behavior (non-reinforced active lever pressing) was then assessed in the previously cocaine-paired and extinction contexts after JNJ16259685 (mGluR1 antagonist: 0.0, 0.6, or 30 pg/0.3 µl/hemisphere) or CNQX (AMPA/kainate receptor antagonist: 0.0, 0.03, or 0.3 µg/0.3 µl /hemisphere) administration into the NAC core, medial or lateral NAC shell, or the ventral caudate-putamen (vCPu, anatomical control). JNJ16259685 or CNQX in the NAC core dose-dependently impaired contextual cocaine-seeking behavior relative to vehicle. Conversely, CNQX, but not JNJ16259685, in the lateral or medial NAC shell attenuated, whereas CNQX or JNJ16259685 in vCPu failed to inhibit, this behavior. The manipulations failed to alter instrumental behavior in the extinction context, general motor activity or food-reinforced instrumental behavior in control experiments. Thus, glutamate-mediated changes in drug context-induced motivation for cocaine involve distinct neuropharmacological mechanisms within the core and shell subregions of the NAC, with the stimulation of mGlu1 and AMPA/kainate receptors in the NAC core and the stimulation of AMPA/kainate, but not mGlu1, receptors in the NAC shell being necessary for this phenomenon.
伏隔核（NAC）核心和壳的功能完整性是可卡因寻求行为在药物复发性的重新激活动物模型中的必要条件；然而，这一现象背后的神经药理学机制还知之甚少。本研究评估了代谢型谷氨酸受体 1 型（mGluR1）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/ kainate 受体群体对药物诱导的可卡因寻求行为重新激活的贡献。大鼠接受训练，在特定环境中按压杠杆以获得无信号的可卡因输注，然后在不同环境中接受消退训练。然后，在之前的可卡因配对和消退环境中评估可卡因寻求行为（无强化主动杠杆按压），在 NAC 核心、内侧或外侧 NAC 壳或腹侧尾壳核（vCPu，解剖对照）中给予 JNJ16259685（mGluR1 拮抗剂：0.0、0.6 或 30 pg/0.3 µl/半球）或 CNQX（AMPA/kainate 受体拮抗剂：0.0、0.03 或 0.3 µg/0.3 µl/半球）后。JNJ16259685 或 CNQX 在 NAC 核心中的剂量依赖性地损害了相对于载体的上下文可卡因寻求行为。相反，CNQX 但不是 JNJ16259685，在外侧或内侧 NAC 壳中减弱了，而 CNQX 或 JNJ16259685 在 vCPu 中未能抑制这种行为。这些操作并未改变在消退环境中的仪器行为，在对照实验中也未改变一般运动活动或食物强化仪器行为。因此，谷氨酸介导的药物环境引起的可卡因动机变化涉及 NAC 核心和壳亚区中的不同神经药理学机制，NAC 核心中的 mGlu1 和 AMPA/kainate 受体的刺激以及 NAC 壳中的 AMPA/kainate 但不是 mGlu1 受体的刺激对于这种现象是必要的。
