Role of serotonergic 5-HT_2A receptors in the psychotomimetic actions of phencyclidine

The psychotomimetic phencydidine (PCP) alters various behavioural responses involving the serotonergic system including potentiating the discriminative stimulus effects of the phenethylamine hallucinogen, 2,5-dimethoxy-4-methylamphetamine (DOM). The present study was undertaken to test the hypothesis that PCP directly interacts with the 5-HT_2A receptor. PC12 cells, a neuronal cell line, were stably transfected with the cDNA encoding the rat 5-HT_2A receptor (PC12-5-HT_2A). In these cells PCP and the related compounds, ketamine and dizocilpine, did not increase [³H]inositol phosphate generation nor did they alter 5-HT-stimulated phosphoinositide hydrolysis. These compounds also did not display appreciable affinity for the 5-HT_2A receptor labelled with [³H]ketanserin. The present study indicates that the behavioural responses to PCP, ketamine and dizocilpine do not involve a direct interaction of these compounds with the 5-HT_2A receptor.