CEREBELLAR VERMIS INVOLVEMENT IN COCAINE-RELATED BEHAVIORS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。虽然小脑越来越多地被视为参与认知的大脑区域，但它通常被排除在被认为介导兴奋剂相关行为的回路之外，因为它的多巴胺含量很低。然而，灵长类动物小脑蚓部（小叶II-III和VIII-IX）已被报道含有轴突多巴胺转运蛋白免疫反应性（DAT-IR）。我们假设，DAT-IR-包含蚓部地区将被激活可卡因滥用者可卡因相关的线索，并在健康的人，将积累DAT-选择性配体。我们使用BOLD功能磁共振成像来确定可卡因相关的线索是否激活可卡因滥用者的DAT-IR富集的蚓部区域，并使用正电子发射断层扫描成像来确定DAT选择性配体（（11）C）阿托烷是否在这些蚓部区域积累。结果如下：可卡因相关的线索选择性地诱导BOLD激活小叶II-III和VIII-IX可卡因用户，并在配体管理后的早期时间点，我们发现可观的（11）C）altropane积累小叶VIII-IX，可能表明DAT存在于这一地区。讨论：这些数据表明小脑蚓部的部分介导可卡因的持续和急性效应。根据先前的研究结果，说明了蚓部连接到中脑多巴胺细胞体区域，确立了蚓部作为感觉运动整合和运动规划的场所的作用，以及物质滥用者在奖励相关和其他认知任务中增加蚓部激活的研究结果，我们建议将蚓部视为可卡因和其他激励相关行为的结构之一。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand ((11)C)altropane accumulated in those vermis regions. Results: Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable ((11)C)altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. Discussion: These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine- and other incentive-related behaviors.