To analyze the mechanisms of PCP abuse, we investigated the changes in PCP-induced motivational properties and neuronal functions in animals. First, we determined that PCP-induced withdrawal syndrome may, in part, be produced by 5-HTergic neuronal systems. Second, using rats treated with subacute PCP, we established that subacute PCP may produce behavioral changes (stereotyped behaviors and hyperlocomotion), mediated by both dopaminergic, 5-HTergic neuronal, and NO systems. Third, using the place conditioning paradigm, we confirmed that (1) both dopamine-D1 and 5-HT2A receptors, but not sigma receptors, may be involved in PCP-induced place aversion, and (2) subacute PCP produces place preference. Finally, we demonstrated that subacute PCP may produce neurochemical changes (the number of 5-HT2A receptors, dopamine turnover, NO synthesis, and immediate early gene expression). These results suggested that several neuronal changes may be related to behavioral changes induced by subacute PCP. Furthermore, it is hypothesized that the alternations of several neuronal systems may establish PCP abuse via the changes of the immediate early gene expression and NO activity induced by subacute PCP treatment. Further studies using receptor selective ligands and sensitive probes that could associate with the pharmacological actions of PCP may elucidate the mechanisms of PCP abuse.