Center for Studies in Behavioral Neurobiology/FRQS Groupe de recherche en neurobiologie comportementale, Department of Psychology, Concordia University, Quebec, Montreal, Canada.
Neuropsychopharmacology. 2019 Aug;44(9):1524-1533. doi: 10.1038/s41386-019-0335-6. Epub 2019 Feb 8.
Preclinical data have shown that the excitatory metabotropic Gα-coupled glutamate receptor, mGluR5, has a role in substance abuse and relapse. However, little is known about the contribution of mGluR5 to the expression of conditioned responding elicited by appetitive Pavlovian cues. We investigated this question in rats that were trained to associate a discrete, auditory conditioned stimulus (CS) with a fructose-glucose solution (5.5% fructose/4.5% glucose; "sugar"). In subsequent tests for the expression of conditioned responding without sugar delivery, CS-elicited fluid port entries were elevated in a context associated with sugar, relative to an equally familiar, neutral context. Inhibiting mGluR5 via systemic injections of a negative allosteric modulator (MTEP; 5 mg/kg) reduced CS port entries in both the sugar context and neutral context. Targeting MTEP microinjections (3 µg/side; 0.3 µl/min) to the nucleus accumbens (Acb) core had no effect on CS port entries at test, whereas the same manipulation in the basolateral amygdala (BLA) produced effects that were topographically dependent. Specifically, microinjecting MTEP in the posterior BLA had no effect on behavior, whereas inhibiting mGluR5 in the anterior BLA enhanced the contextual discrimination of CS port entries. These data are the first to show a role of mGluR5 in the context-dependent expression of appetitive Pavlovian conditioned responding, with a topographically defined arrangement of mGluR5 in the BLA being particularly important for context-based responding to a discrete, appetitive cue.
临床前数据表明，兴奋性代谢型谷氨酸受体 mGluR5 在物质滥用和复发中起作用。然而，对于 mGluR5 对由奖赏性巴甫洛夫线索引起的条件反应表达的贡献知之甚少。我们在接受训练以将离散的听觉条件刺激 (CS) 与果糖-葡萄糖溶液 (5.5% 果糖/4.5% 葡萄糖；“糖”) 相关联的大鼠中研究了这个问题。在没有糖输送的条件反应表达的后续测试中，与同样熟悉的中性环境相比，与糖相关联的环境中 CS 诱发的液体端口进入增加。通过全身注射负变构调节剂 (MTEP；5 mg/kg) 抑制 mGluR5 会降低糖环境和中性环境中的 CS 端口进入。将 MTEP 微注射（3 µg/侧；0.3 µl/min）靶向伏隔核 (Acb) 核心对测试中的 CS 端口进入没有影响，而在杏仁核基底外侧核 (BLA) 中进行相同的操作则产生了与地形相关的影响。具体而言，在 BLA 后区微注射 MTEP 对行为没有影响，而在前区 BLA 中抑制 mGluR5 则增强了 CS 端口进入的上下文辨别。这些数据首次表明 mGluR5 在奖赏性巴甫洛夫条件反应的上下文依赖表达中的作用，BLA 中 mGluR5 的地形定义排列对于离散的、奖赏性线索的基于上下文的反应尤为重要。
