Histological analyses of reinforcement circuitry

强化电路的组织学分析

• 批准号: 7321127
• 负责人: SATOSHI IKEMOTO
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7321127
• 关键词: Histological; analyses; reinforcement; circuitry

Our major aim of this project is to determine detailed neural connections involved in drug reinforcement. Behavioral studies indicate that the mesolimbic dopamine system is functionally heterogeneous. The medial portion of the ventral striatum, which includes the medial accumbens shell and medial olfactory tubercle, is more responsible for primary reinforcing effects of psychomotor stimulants than the lateral ventral striatum, which includes the accumbens core, ventral shell, and lateral tubercle. In the dopamine cell-body region, the posterior VTA and the central linear nucleus raphe are more responsible than the anterior VTA for the reinforcing effects of a number of drugs including opiates and cholinergic agents. Based on these behavioral findings, we hypothesize that the reward-trigger zones in the ventral striatum (i.e., the medial accumbens shell and medial olfactory tubercle) receives projections from the reward-trigger zones in the ventral midbrain (i.e., the posterior VTA and central linear nucleus). When the retrograde tracer Fluorogold (FG) was deposited into the medial ventral striatum (the medial shell or medial tubercle), FG-filled cells were found largely in the posteromedial compartment of the VTA and the central linear nucleus. On the other hand, when FG was deposited into the lateral ventral striatum (the core, lateral shell, or lateral tubercle), FG-filled cells were found mostly in the lateral portion of the VTA. Our results suggest that the reward-trigger zones in the medial ventral striatum receive input from the reward-trigger zones in the posteromedial ventral midbrain.

我们这个项目的主要目的是确定药物强化涉及的详细神经连接。行为研究表明中脑边缘多巴胺系统在功能上是异质的。腹侧纹状体的内侧部分（包括内侧伏隔核和内侧嗅结节）比外侧腹侧纹状体（包括伏隔核、腹侧壳和外侧结节）更能发挥精神运动兴奋剂的主要增强作用。在多巴胺细胞体区域，后 VTA 和中央线状中缝核比前 VTA 更能增强包括阿片类药物和胆碱能药物在内的多种药物的作用。基于这些行为发现，我们假设腹侧纹状体中的奖赏触发区（即内侧伏隔核和内侧嗅结节）接收来自腹侧中脑奖赏触发区（即后VTA和中央线性核）的投射。当逆行示踪剂 Fluorogold (FG) 沉积到内侧腹侧纹状体（内侧壳或内侧结节）时，在 VTA 的后内侧室和中央线状核中发现了大量充满 FG 的细胞。另一方面，当 FG 沉积到侧腹侧纹状体（核心、侧壳或侧结节）时，FG 填充的细胞主要发现于 VTA 的外侧部分。我们的结果表明，内侧腹侧纹状体中的奖励触发区接收来自后内侧腹侧中脑的奖励触发区的输入。