Differential and region-specific activation of mitogen-activated protein kinases following chronic administration of phencyclidine in rat brain.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology March 1, 2001 S V Kyosseva, S M Owens, A D Elbein et al.
Chronic administration of the NMDA receptor antagonist phencyclidine (PCP) in rats activates the ERK signaling pathway specifically in the cerebellum, but not in other brain regions. Using osmotic pumps to deliver PCP continuously for 10 or 20 days at 18 mg/kg/day, phosphorylation of ERK1, ERK2, and MEK increased significantly in the cerebellum, with no change at 3 days. Dose-dependent elevation of ERK1 and ERK2 phosphorylation occurred in the cerebellum at 2.5, 10, 18, or 25 mg/kg/day over 10 days, while JNK and p38 activities remained unchanged across all brain regions examined. These findings suggest a role for ERK signaling in PCP's effects and possibly in schizophrenia.