Role of serotonergic 5-HT2A receptors in the psychotomimetic actions of phencyclidine

The psychotomimetic phencyclidine (PCP) alters various behavioural response s involving the serotonergic system including potentiating the discriminati ve stimulus effects of the phenethylamine hallucinogen, 2,5-dimethoxy-4-met hylamphetamine (DOM), The present study was undertaken to test the hypothes is that PCP directly interacts with the 5-HT2A receptor. PC12 cells, a neur onal cell line, were stably transfected with the cDNA encoding the rat 5-HT 2A receptor (PC12-5-HT2A). In these cells PCP and the related compounds, ke tamine and dizocilpine, did not increase [H-3]inositol phosphate generation nor did they alter 5-HT-stimulated phosphoinositide hydrolysis. These comp ounds also did not display appreciable affinity for the 5-HT2A receptor lab elled with [H-3]ketanserin. The present study indicates that the behavioura l responses to PCP, ketamine and dizocilpine do not involve a direct intera ction of these compounds with the 5-HT2A receptor.