NEUROBIOLOGY OF COCAINE ABUSE DETECTED BY FUNCTIONAL MRI

功能性 MRI 检测可卡因滥用的神经生物学

• 批准号: 7375060
• 负责人: Shi-Jiang Li
• 金额: $ 1.22万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375060
• 关键词: NEUROBIOLOGY; COCAINE; ABUSE; DETECTED; FUNCTIONAL

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. 1) The Neural Correlates for Shifting the neutral Nature of Drug Stimuli to be the Predictors of Drug Rewards in the Human Brain. Seventeen human cocaine users and eighteen control human subjects successfully participated in the cocaine-cue elicited cocaine craving study by using functional MRI (fMRI) method. The content-specificity and population specificity indicated that cocaine-cue films successfully elicited subjective craving and activated two groups of the addiction-encoded neural correlates. One group is associated with the psychological arousal, episodic memory retrieval, attention, and behavioral planning in the prefrontal (such as in Brodmann Area 10), temporal and occipital cortex. The other group is positively correlated with the cocaine craving rating, such as in the subcollosal cortex (SCC) and the anterior medial orbitofrontal cortex (amOFC). Our results demonstrate that the neural correlates in the SCC have shifted the environmental drug stimuli from their neutral nature to the predictors of cocaine rewards. The neurobiological mechanisms responsible for such a shift may be the completion of a functional establishment in SCC from an unconditioned reward detector to conditioned reward predictor due to the over-learning of the cue-drug pairing, a key neurobiological characteristic of the addiction. It is suggested that the activated signal in the amOFC region represent the motivational potential and the craving is the manifestation of this motivational potential that drives the drug seeking and taking behavior. 2) Neural Responses to Acute Cocaine Administration in the Human Brain Detected by fMRI. Understanding the neurobiological processes responsible for the altered behaviors that drives drug-taking behavior is a central challenge in addiction research. With an improved functional MRI (fMRI) method for detecting a blood oxygenation level dependent (BOLD) contrast, we report that acute cocaine administration to human cocaine users concurrently activates the mesolimbic and mesocortical dopaminergic projections, which in turn may gate the hierarchical brain networks in anterior prefrontal cortex (aPFC) of the Brodmann Area 10 (BA10) and orbitofrontal cortex (OFC) that mediate associative learning, motivation and memory. It is suggested that the negative BOLD responses in the mesocorticolimbic dopaminergic circuitry represent the bottom-up reward encoding processes essential for drug-induced acquisition of addictive behavior, whereas the positive BOLD signal in the BA10 and OFC regions represents the bottom-up addiction encoding processes that repeated cocaine use could repeatedly initiate to strengthen this learned association into a state of addiction.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 1）将药物刺激的中性性质转变为人脑药物奖励预测因子的神经相关性。 17 名人类可卡因使用者和 18 名对照人类受试者使用功能性 MRI (fMRI) 方法成功参与了可卡因提示引发可卡因渴望研究。 内容特异性和人群特异性表明可卡因提示电影成功地引发了主观渴望并激活了两组成瘾编码的神经相关物。其中一组与前额叶（例如布罗德曼 10 区）、颞叶和枕叶皮层的心理唤醒、情景记忆检索、注意力和行为规划有关。另一组与可卡因渴望等级呈正相关，例如在胶体下皮质（SCC）和前内侧眶额皮质（amOFC）中。我们的结果表明，SCC 中的神经相关因素已将环境药物刺激从中性性质转变为可卡因奖励的预测因素。造成这种转变的神经生物学机制可能是由于提示药物配对的过度学习（成瘾的关键神经生物学特征）而完成的，从无条件奖励检测器到条件奖励预测器的 SCC 功能建立。表明amOFC区域的激活信号代表动机潜力，渴望是这种动机潜力的表现，驱动寻药和吸毒行为。 2) 通过功能磁共振成像检测人脑对急性可卡因给药的神经反应。了解导致吸毒行为改变的神经生物学过程是成瘾研究的一个核心挑战。通过改进的功能性磁共振成像（fMRI）方法来检测血氧水平依赖性（BOLD）对比度，我们报告说，对人类可卡因使用者进行急性可卡因注射同时激活中脑边缘和中皮质多巴胺能投射，这反过来可能会门控分层大脑网络布罗德曼 10 区 (BA10) 的前额叶皮质 (aPFC) 和调节联想的眶额皮质 (OFC)学习、动机和记忆。中皮质边缘多巴胺能回路中的负 BOLD 反应代表了药物诱导获得成瘾行为所必需的自下而上的奖励编码过程，而 BA10 和 OFC 区域中的正 BOLD 信号代表了自下而上的成瘾编码过程反复使用可卡因可能会反复引发这种习得性关联，从而导致成瘾状态。