Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy -: a [123I]CNS-1261 SPET study
Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy -: a [123I]CNS-1261 SPET study
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DOI：
10.1007/s00213-007-1047-x
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Pilowsky, Lyn S.
中科院分区：
文献类型：
--
作者：
Stone, James M.;Erlandsson, Kjell;Pilowsky, Lyn S.
氯胺酮诱导类似精神分裂症的阳性和阴性精神病症状的作用。这些被认为是通过其作为N-甲基-D-天冬氨酸（NMDA）受体的非竞争性拮抗剂的作用而产生的。目的我们使用[I-123]CNS-1261研究氯胺酮与健康人对照体内NMDA受体的结合及其与阳性和阴性精神病症状诱导的关系。材料和方法10名健康对照进行了两次[I-123]CNS-1261单光子发射断层扫描。1261.在每种情况下，他们接受氯胺酮或生理盐水的推注。在每次扫描结束时进行简明精神病评定量表（BPRS）。使用预定义的感兴趣区域估计氯胺酮给药后[I-123]CNS-1261的分布容积变化。两个正常的皮质结合指数也被用来研究氯胺酮对NMDA受体可用性的影响，按区域，校正后的全球和非特异性effects.Results氯胺酮诱导的减少[I-123]CNS-1261在所有区域的分布容积显示出最强的相关性与BPRS负分量表（p < 0.01）。在正常皮层测量中，中下额叶皮层NMDA受体结合率与BPRS阴性分量表呈显著相关（BI 1 r=0.88，BI 2 r=95.9，p < 0.001）。结论氯胺酮可调节[I-123]CNS-1261的结合率，氯胺酮是一种已知在体外竞争NMDA受体上相同位点的药物。氯胺酮可能通过直接抑制NMDA受体诱导阴性症状，阳性症状可能通过不同的神经化学途径产生。
Rationale Ketamine induces effects resembling both positive and negative psychotic symptoms of schizophrenia. These are thought to arise through its action as an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor.Objectives We used [I-123]CNS-1261 to study ketamine binding to NMDA receptors in healthy human controls in vivo and its relationship to positive and negative psychotic symptom induction.Materials and methods Ten healthy controls underwent two single-photon emission tomography scans with [I-123]CNS-1261. On each occasion, they received a bolus infusion of either ketamine or saline. The Brief Psychiatric Rating Scale (BPRS) was administered at the end of each scan. Predefined regions of interest were used to estimate change in volume of distribution of [I-123]CNS-1261 following ketamine administration. Two normalised-to-cortex binding indices were also used in order to study effects of ketamine on NMDA receptor availability by region, after correction for global and nonspecific effects.Results Ketamine-induced reduction in [I-123]CNS-1261 volume of distribution in all regions showed the strongest correlation with BPRS negative subscale (p < 0.01). With the normalised-to-cortex measures, NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale (BI1 r=0.88, BI2 r=95.9, p < 0.001).Conclusions [I-123]CNS-1261 binding was modulated by ketamine, a drug known to compete for the same site on the NMDA receptor in vitro. Ketamine may induce negative symptoms through direct inhibition of the NMDA receptor, and positive symptoms may arise through a different neurochemical pathway.