González-Maeso Javier, Sealfon Stuart C
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Trends Neurosci. 2009 Apr;32(4):225-32. doi: 10.1016/j.tins.2008.12.005. Epub 2009 Mar 5.
Research on psychedelics such as lysergic acid diethylamide (LSD) and dissociative drugs such as phencyclidine (PCP) and the symptoms, neurochemical abnormalities and treatment of schizophrenia have converged. The effects of hallucinogenic drugs resemble some of the core symptoms of schizophrenia. Some atypical antipsychotic drugs were identified by their high affinity for serotonin 5-HT(2A) receptors, which is also the target of LSD-like drugs. Several effects of PCP-like drugs are strongly affected by both 5-HT(2A) and metabotropic glutamate 2/3 receptor modulation. A serotonin-glutamate receptor complex in cortical pyramidal neurons has been identified that might be the target both of psychedelics and the atypical and glutamate classes of antipsychotic drugs. Recent results on the receptor, signalling and circuit mechanisms underlying the response to psychedelic and antipsychotic drugs might lead to unification of the serotonin and glutamate neurochemical hypotheses of schizophrenia.
对诸如麦角酸二乙酰胺(LSD)之类的致幻剂以及诸如苯环己哌啶(PCP)之类的解离性药物的研究,与对精神分裂症的症状、神经化学异常及治疗的研究已经融合在一起。致幻药物的作用类似于精神分裂症的一些核心症状。一些非典型抗精神病药物因其对5-羟色胺5-HT(2A)受体具有高亲和力而被识别出来,而该受体也是类似LSD药物的作用靶点。PCP类药物的几种作用受到5-HT(2A)和代谢型谷氨酸2/3受体调节的强烈影响。已确定皮质锥体细胞中的一种5-羟色胺-谷氨酸受体复合物可能是致幻剂以及非典型和谷氨酸类抗精神病药物的共同靶点。最近关于致幻剂和抗精神病药物反应背后的受体、信号传导和回路机制的研究结果,可能会使精神分裂症的5-羟色胺和谷氨酸神经化学假说得到统一。