Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study
Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study
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DOI：
10.1007/s00213-006-0690-y
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Walter, Henrik
中科院分区：
文献类型：
--
作者：
Abler, Birgit;Erk, Susanne;Walter, Henrik
奥氮平是一种广泛用于治疗精神分裂症和双相情感障碍的抗精神病药物。虽然人们早就知道多巴胺系统的调节是神经阻滞剂作用的基本机制，但它们对多巴胺介导的奖励功能的影响仍然知之甚少。目的利用功能性磁共振成像（fMRI），揭示单剂量奥氮平对脑奖励相关激活的影响。方法采用双盲交叉设计，对8名健康受试者进行2次扫描，分别在服用奥氮平5 mg后5 h和服用安慰剂后5 h进行扫描。实验对象采用金钱奖励的延迟激励模式来研究奖励功能，采用高碳酸血症挑战的屏气任务来揭示非特异性药物对fMRI信号的影响。结果与安慰剂相比，奥氮平降低了腹侧纹状体、前扣带和下额叶皮层的奖励相关脑激活。只有腹侧纹状体的差异效应（高>无奖励）独立于整体药物效应，通过屏气任务进行测量。与腹侧纹状体的差异效应相似，在高奖励的实验中，反应时间的加速在奥氮平组中被减弱。我们的行为和功能磁共振成像结果可以解释为神经影像学的第一个证据，证明奥氮平会影响多巴胺能脑区差异激活和反应时间加速所代表的激励显著性分配。这有助于更好地理解抗精神病药物在精神疾病中的作用。此外，我们证明了高碳酸血症挑战在功能药物mri中的价值。
Rationale Olanzapine is a neuroleptic drug widely prescribed to treat schizophrenia and bipolar disorder. Although it is long known that modulation of the dopamine system is a basic mechanism of action of neuroleptics, their impact on reward functions mediated by dopamine is still poorly understood.Objective Using functional magnetic resonance imaging (fMRI), we intended to reveal the effects of a single dose of olanzapine on reward-related brain activation.Methods Eight healthy subjects were each scanned twice, once 5 h after intake of 5 mg of olanzapine and once after intake of placebo in a double-blind cross-over design. Subjects performed a delayed incentive paradigm with monetary reward to investigate reward functions and a breath-holding task as a hypercapnic challenge to reveal unspecific drug effects on the fMRI signal.Results Reward-related brain activation in the ventral striatum, anterior cingulate and inferior frontal cortex was reduced on olanzapine compared to placebo. Only the differential effects (high > no reward) in the ventral striatum were independent of overall drug effects as measured with the breath-holding task. Parallel to the differential effects in the ventral striatum, the acceleration of reaction times in the trials with higher rewards was diminished in the olanzapine sessions.Conclusions Our behavioural and fMRI results can be interpreted as first evidence from neuroimaging that olanzapine affects the assignment of incentive salience represented by differential activation in dopaminergic brain areas and acceleration of reaction times. This can help to better understand neuroleptic effects in psychiatric diseases. Furthermore, we demonstrate the value of a hypercapnic challenge in functional pharmaco-MRI.