Sharp J W
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan 66506, USA.
Brain Res. 1997 May 30;758(1-2):51-8. doi: 10.1016/s0006-8993(97)00025-5.
Phencyclidine (PCP) is a compound that results in abnormal human behavior and has been proposed as a chemical model for schizophrenia. It was hypothesized that PCP induction of the immediate-early gene, c-fos, should be seen in areas associated with emotional behavior, such as the cortex and limbic system. It was also proposed that PCP may induce c-fos via the sigma receptor. PCP and two sigma ligands, 1,3-di(2-tolyl)guanidine (DTG) and pentazocine, were shown to induce c-fos in similar patterns. The three compounds abundantly induced c-fos in the cingulate, parietal, and piriform cortices and the midline structures of the thalamus and hypothalamus. Neither PCP nor the sigma ligands induced c-fos in the hippocampus. This suggests that PCP binding at NMDA receptors does not result in significant c-fos induction. Rimcazole, a putative sigma2 receptor antagonist, and other sigma ligands have been shown to ameliorate PCP stereotypic behavior. Rimcazole inhibited PCP c-fos induction in the cingulate and parietal cortices and DTG c-fos induction in the cingulate cortex. DTG shows both sigma1 and sigma2 binding affinity. Rimcazole failed to inhibit pentazocine c-fos induction. Pentazocine binds only to sigma1 receptors. This suggests that PCP may produce a significant fraction of its c-fos induction via sigma2 receptors.
苯环己哌啶（PCP）是一种可导致人类行为异常的化合物，已被提议作为精神分裂症的化学模型。据推测，在与情绪行为相关的区域，如皮层和边缘系统中，应该能观察到PCP诱导即刻早期基因c-fos的表达。还有人提出，PCP可能通过σ受体诱导c-fos。PCP以及两种σ配体，1,3-二（2-甲苯基）胍（DTG）和喷他佐辛，被证明以相似的模式诱导c-fos。这三种化合物在扣带回、顶叶和梨状皮层以及丘脑和下丘脑的中线结构中大量诱导c-fos。PCP和σ配体均未在海马体中诱导c-fos。这表明PCP与N-甲基-D-天冬氨酸（NMDA）受体结合不会导致显著的c-fos诱导。利咪唑是一种假定的σ2受体拮抗剂，其他σ配体已被证明可改善PCP的刻板行为。利咪唑抑制了PCP在扣带回和顶叶皮层中的c-fos诱导以及DTG在扣带回皮层中的c-fos诱导。DTG显示出对σ1和σ2的结合亲和力。利咪唑未能抑制喷他佐辛的c-fos诱导。喷他佐辛仅与σ1受体结合。这表明PCP可能通过σ2受体产生其很大一部分的c-fos诱导作用。
