The effects of intraperitoneally (IP) injected phencyclidine (phencyclohexyl piperidine; PCP) on the metabolism of dopamine (DA) and cholecystokinin-like immunoreactivity (CCK-LI) in the rat brain were investigated in connection with PCP-induced behavioral changes. The predominant behavior change elicited by 2.5 mg/kg PCP was locomotion, while with higher doses (5 and 10 mg/kg) sniffing, swaying and falling were observed in addition to the enhanced locomotor activity. Backpedaling and rotation were observed in 10 mg/kg PCP-treated rats. IP injection of PCP caused a dose-related increase in the levels of DA and 3,4-dihydroxy-phenylacetic acid (DOPAC) in the medial frontal cortex (MFC) and anterior cingulate cortex (ant.CC) without any changes in the nucleus accumbens (NAc) or striatum. CCK-LI in the MFC, ant.CC and NAc was decreased in a dose-dependent manner following IP injection of PCP. These findings support the evidence that PCP selectively activates the mesocortical DA systems. Furthermore, our results indicate a functional relationship between the mesocortical DA neurons and intrinsic CCK containing cortical neurons, and the change in the activity of the intrinsic CCK-containing cortical neurons in these two areas, perhaps due to an alteration in DA transmission, might be involved in behavioral changes after PCP injection.