Neural Mechanisms of Individual Differences in Cocaine Avoidance

摘要： 滥用毒品，如可卡因，会产生有益的效果，已进行了广泛的调查。然而， 这些药物还会产生人们知之甚少的不良反应，尽管它们强烈地影响着 寻求毒品，并表现出很大的个体差异性，这导致了个体成瘾的差异 倾向性。我们发现对可卡因的厌恶反应严重依赖于5-羟色胺和谷氨酸。 被盖旋转内侧核(RMTg)是中脑多巴胺神经元的主要传入神经。这 Proposal研究了这些受体驱动神经激活和厌恶的细胞机制 条件反射，以及为什么这些反应在一些人身上比其他人发生得更强烈， 为规范药物寻找和治疗寻找新的潜在治疗靶点的总体目标 上瘾。

Abstract: Drugs of abuse, such as cocaine, produce rewarding effects that have been extensively investigated. However, these drugs also produce aversive effects that are far less understood, even though they strongly influence drug‐seeking, and exhibit large individual variability that contributes to differences in individual addiction propensity. We found that aversive responses to cocaine depend critically on serotonin and glutamate signaling in the rostromedial tegmental nucleus (RMTg), a major afferent to midbrain dopamine neurons. This proposal examines cellular mechanisms by which these receptors drive neural activation and aversive conditioning, and why these responses occur much more strongly in some individuals than others, with an overall aim of identifying novel potential therapeutic targets for regulating drug‐seeking and treating addiction.