Schmidt A, Denier N, Magon S, Radue E-W, Huber C G, Riecher-Rossler A, Wiesbeck G A, Lang U E, Borgwardt S, Walter M
1] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland [2] Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
Transl Psychiatry. 2015 Mar 24;5(3):e533. doi: 10.1038/tp.2015.28.
Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.
已知纹状体中的强化信号对于介导急性药物摄入的主观奖赏效应至关重要。有人提出，这些效应可能更多地参与药物成瘾的早期阶段，而负性强化效应可能更多地发生在疾病的后期阶段。本研究使用静息态功能磁共振成像来探究急性海洛因替代是否也会在长期使用海洛因维持治疗的患者的纹状体脑区诱导正性强化效应。使用独立成分分析和双回归方法，我们比较了一组接受海洛因急性输注和安慰剂的海洛因依赖患者以及仅接受安慰剂的20名健康受试者在基底神经节/边缘网络内的静息态功能连接（rsFC）强度。随后进行相关分析，以测试海洛因暴露下的rsFC强度是否与主观奖赏效应以及海洛因及其主要代谢产物吗啡的血浆浓度相关。相对于患者的安慰剂治疗，海洛因显著增加了基底神经节/边缘网络内左侧壳核的rsFC，其增加程度与患者的快感以及吗啡的血浆水平呈正相关。此外，相对于患者的安慰剂治疗，健康对照组在该网络中显示后扣带回皮质/楔前叶的rsFC增加。我们的结果表明，急性海洛因替代通过增加海洛因依赖患者的纹状体连接性诱导主观奖赏效应，表明在长期维持治疗后纹状体中的正性强化效应仍然存在。
