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小脑在药物线索关联记忆中的作用:与内侧前额叶皮质的功能相互作用。

The role of the cerebellum in drug-cue associative memory: functional interactions with the medial prefrontal cortex.

作者信息

Gil-Miravet Isis, Guarque-Chabrera Julian, Carbo-Gas Maria, Olucha-Bordonau Francisco, Miquel Marta

机构信息

Área de Psicobiología, Universitat Jaume I, Castellón de la Plana, Spain.

INSERM U1215, Pathophysiology of Addiction, NeuroCentre Magendie, Bordeaux, France.

出版信息

Eur J Neurosci. 2019 Aug;50(3):2613-2622. doi: 10.1111/ejn.14187. Epub 2018 Oct 24.

Abstract

Drug-induced Pavlovian memories are thought to be crucial for drug addiction because they guide behaviour towards environments with drug availability. Drug-related memory depends on persistent changes in dopamine-glutamate interactions in the medial prefrontal cortex (mPFC), basolateral amygdala, nucleus accumbens core and hippocampus. Recent evidence from our laboratory indicated that the cerebellum is also a relevant node for drug-cue associations. In the present study, we tested the role that specific regions of the cerebellum and mPFC play in the acquisition of cocaine-induced preference conditioning. Quinolinic acid was used to manage a permanent deactivation of lobule VIII in the vermis prior to conditioning. Additionally, lidocaine was infused into the prelimbic and infralimbic (IL) cortices for reversible deactivation before every training session. The present findings show, for the first time, that the cerebellum and mPFC might act together in order to acquire drug-cue Pavlovian associations. Either a dorsal lesion in lobule VIII or an IL deactivation encouraged cocaine-induced preference conditioning. Moreover, simultaneous IL-cerebellar deactivation prevented the effect of either of the separate deactivations. Therefore, similar to the IL cortex, neural activity in the cerebellum may be crucial for ensuring inhibitory control of the expression of cocaine-related memories.

摘要

药物诱导的巴甫洛夫记忆被认为对药物成瘾至关重要,因为它们引导行为趋向于有药物可得的环境。与药物相关的记忆依赖于内侧前额叶皮质(mPFC)、基底外侧杏仁核、伏隔核核心和海马体中多巴胺 - 谷氨酸相互作用的持续变化。我们实验室最近的证据表明,小脑也是药物线索关联的一个相关节点。在本研究中,我们测试了小脑和mPFC的特定区域在可卡因诱导的偏好条件反射习得中所起的作用。在条件反射之前,使用喹啉酸使蚓部小叶VIII永久失活。此外,在每次训练前,将利多卡因注入前额叶和边缘下(IL)皮质以进行可逆性失活。本研究结果首次表明,小脑和mPFC可能共同作用以习得药物线索巴甫洛夫关联。小叶VIII的背侧损伤或IL失活都会促进可卡因诱导的偏好条件反射。此外,同时进行IL - 小脑失活可防止单独失活的任何一种效果。因此,与IL皮质类似,小脑中的神经活动对于确保对可卡因相关记忆表达的抑制控制可能至关重要。

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