Ceruletide inhibits phencyclidine-induced dopamine and serotonin release in rat prefrontal cortex

Phencyclidine (PCP; 5.0 mg/kg, IF) produced a greater increase in extracellular dopamine (DA) levels in the prefrontal cortex than in the striatum, while PCP increased the extracellular 5-hydroxytryptamine (serotonin; 5-HT) levels in the prefrontal cortex but not the striatum, as determined by in vivo microdialysis in awake, freely moving rats. The cholecystokinin (CCK)-related decapeptide ceruletide (120 and 400 mu g/kg, IF), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in the extracellular levels of DA and 5-HT in the prefrontal cortex, but not in the striatum. These effects were reversed by PD 135,158, a selective CCK-B receptor antagonist (0.1 mg/kg, SC), administered 5 min prior to ceruletide. When administered alone, ceruletide (400 mu g/kg, IF) significantly increased basal extracellular DA levels only in the prefrontal cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (0.5 mg/kg, IF) also increased extracellular DA levels in the prefrontal cortex, but this effect was unaffected by ceruletide pretreatment. These results suggest that ceruletide may differentially modulate basal and PCP-induced release of DA and 5-HT in the prefrontal cortex. (C) 1998 Elsevier Science Inc.