Department Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Psychopharmacology (Berl). 2013 Sep;229(2):219-26. doi: 10.1007/s00213-013-3105-x. Epub 2013 Apr 19.
Release of dopamine in the nucleus accumbens (NAcc) is essential for acute drug reward. The present study was designed to trace the reinforcing effect of dopamine release by measuring the functional connectivity (FC) between the NAcc and brain regions involved in a limbic cortical-subcortical circuit during a dopaminergic challenge. Twenty healthy volunteers received single doses of methylphenidate (40 mg) and placebo on separate test days according to a double-blind, cross-over study design. Resting state functional magnetic resonance imaging (fMRI) was measured between 1.5 and 2 h postdosing. FC between regions of interest (ROI) in the NAcc, the medial dorsal nucleus (MDN) of the thalamus and remote areas within the limbic circuit was explored. Methylphenidate significantly reduced FC between the NAcc and the basal ganglia (i.e., subthalamic nucleus and ventral pallidum (VP)), relative to placebo. Methylphenidate also decreased FC between the NAcc and the medial prefrontal cortex (mPFC) as well as the temporal cortex. Methylphenidate did not affect FC between MDN and the limbic circuit. It is concluded that methylphenidate directly affects the limbic reward circuit. Drug-induced changes in FC of the NAcc may serve as a useful marker of drug activity in in the brain reward circuit.
伏隔核（NAcc）中多巴胺的释放对急性药物奖赏至关重要。本研究旨在通过测量多巴胺刺激期间 NAcc 与参与边缘皮质-皮质下回路的脑区之间的功能连接（FC）来追踪多巴胺释放的强化作用。20 名健康志愿者根据双盲、交叉设计在不同的测试日接受单剂量哌甲酯（40mg）和安慰剂。给药后 1.5 至 2 小时测量静息状态功能磁共振成像（fMRI）。探索了 NAcc 与内侧背核（MDN）和边缘回路内远程区域之间的感兴趣区域（ROI）之间的 FC。与安慰剂相比，哌甲酯显著降低了 NAcc 与基底节（即丘脑底核和腹侧苍白球（VP））之间的 FC。哌甲酯还降低了 NAcc 与前额叶皮质内侧（mPFC）和颞叶之间的 FC。MDN 与边缘回路之间的 FC 不受哌甲酯影响。结论是，哌甲酯直接影响边缘奖赏回路。NAcc 的 FC 变化可能是大脑奖赏回路中药物活动的有用标志物。
