Sharp Frank R, Hendren Robert L
Department of Neurology, MIND Institute, University of California at Davis, Wet Labs Room 2416, 2805 50th Street, Sacramento, CA 95817, USA.
Epilepsy Behav. 2007 Jun;10(4):515-20. doi: 10.1016/j.yebeh.2007.02.014. Epub 2007 Apr 6.
Phencyclidine (PCP), ketamine (Special K), and MK-801 are noncompetitive N-methyl-d-aspartate (NMDA) antagonists that produce acute psychosis in humans. The psychosis produced by these psychomimetic drugs is indistinguishable from schizophrenia and includes both positive and negative symptoms. This drug-induced psychosis occurs after puberty in humans. On the basis of the MK-801-induced spike-and-wave activity in rats and increased blood flow and metabolism in brain of patients with psychosis caused by these psychomimetics, this brief review argues that this psychosis is an atypical form of limbic epilepsy. Moreover, there is a specific limbic thalamcortical psychosis circuit that mediates cell injury in limbic cortex of rodents and may mediate this PCP-induced psychosis in humans. It is proposed that this thalamocortical psychosis circuit develops at puberty and can mediate PCP and ketamine-mediated psychosis and possibly the psychosis of schizophrenia, bipolar disease and other disorders that have their onset at puberty. Finally, based on this developmentally regulated psychosis/epilepsy-related thalamocortical circuitry, it is proposed that antiepileptic drugs that promote GABAergic mechanisms may decrease the probability of episodic psychosis from any cause.
苯环己哌啶（PCP）、氯胺酮（Special K）和MK - 801是非竞争性N - 甲基 - D - 天冬氨酸（NMDA）拮抗剂，可在人类中引发急性精神病。这些拟精神病药物引发的精神病与精神分裂症难以区分，包括阳性和阴性症状。这种药物诱发的精神病在人类青春期后出现。基于MK - 801在大鼠中诱发的棘波和慢波活动以及这些拟精神病药物导致的精神病患者大脑中血流量和代谢的增加，本简要综述认为这种精神病是边缘性癫痫的一种非典型形式。此外，存在一个特定的边缘丘脑皮质精神病回路，它介导啮齿动物边缘皮质中的细胞损伤，并且可能介导人类中这种由PCP诱发的精神病。有人提出，这种丘脑皮质精神病回路在青春期发育，可介导PCP和氯胺酮介导的精神病，以及可能介导精神分裂症、双相情感障碍和其他在青春期发病的疾病的精神病。最后，基于这种发育调节的精神病/癫痫相关丘脑皮质回路，有人提出促进GABA能机制的抗癫痫药物可能会降低任何原因引起的发作性精神病的发生概率。
