Vulnerability to psychotogenic effects of ketamine is associated with elevated D2/3-receptor availability
Vulnerability to psychotogenic effects of ketamine is associated with elevated D2/3-receptor availability
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DOI：
10.1017/s1461145712000764
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发表时间：
2013-05-01
影响因子：
4.8
通讯作者：
Gruender, Gerhard
中科院分区：
文献类型：
--
作者：
Vernaleken, Ingo;Klomp, Majken;Gruender, Gerhard
既往采用竞争模式的正电子发射断层扫描（PET）研究显示，在使用致精神病剂量的N-甲基-D-天冬氨酸拮抗剂氯胺酮激发后，纹状体[C-11]-雷氯必利结合无变化或显著下降。我们使用高亲和力配体[F-18]-fallypride（FP）探索氯胺酮诱导的精神病症状的严重程度与整个大脑中多巴胺D-2/3受体可用性改变之间的关系。PET记录是在一组10名健康的年轻男性志愿者中获得的，在安慰剂条件下，在输注氯胺酮的过程中，拟精神病剂量。在这两种情况下的阳性和阴性综合征量表和思维和语言指数的管理揭示了精神分裂症的主要阴性症状的大量出现，持续到3小时PET记录结束。皮质、尾状核和其他脑区的基线Fp结合高度预测氯胺酮条件下精神病症状的个体严重程度。然而，没有证据表明氯胺酮引起的Fp结合减少。在早期研究结果的背景下，我们推测，高基线D-2/3受体的可用性可能会带来好处，认知灵活性，但增加了适应不良的信息处理的风险，面对环境压力和挑战。
Previous positron emission tomography (PET) studies employing competition paradigms have shown either no change or substantial declines in striatal [C-11]-raclopride binding after challenge with psychotogenic doses of the N-methyl-D-aspartate antagonist ketamine. We sought to probe the relationship between the severity of ketamine-induced psychotic symptoms and altered dopamine D-2/3 receptor availability throughout brain using the high affinity ligand [F-18]-fallypride (FP). PET recordings were obtained in a group of 10 healthy, young male volunteers, in a placebo condition, and in the course of an infusion with ketamine at a psychotomimetic dose. Administration of the Positive and Negative Syndrome Scale and the Thought and Language Index in both conditions revealed a substantial emergence of mainly negative symptoms of schizophrenia, persisting until the end of the 3 h PET recordings. The baseline Fp binding in cortex, caudate nucleus and other brain regions was highly predictive of the individual severity of psychotic symptoms in the ketamine condition. However, there was no evidence of ketamine-evoked reductions in Fp binding. In the context of earlier findings, we speculate that high baseline D-2/3-receptor availability may impart benefits with regard to cognitive flexibility, but increases the risk of maladaptive information processing in the face of environmental stresses and challenges.