Phencyclidine (PCP) acts at sigma sites to induce c-fos gene expression.
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.
Sharp
J W
JW
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan 66506, USA. sharp@vet.ksu.edu
D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006179:Gyrus Cinguli / Q000187:drug effects; D007124:Immunoenzyme Techniques; D010622:Phencyclidine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016760:Proto-Oncogene Proteins c-fos; D010622:Phencyclidine