Chronic phencyclidine induces inflammatory responses and activates GSK3β in mice.

Abstract

Use of phencyclidine (PCP) in rodents can mimic some aspects of schizophrenia. However, the underlying mechanism is still unclear. Growing evidence indicates that neuroinflammation plays a significant role in the pathophysiology of schizophrenia. In this study, we focused on inflammatory responses as target of PCP for inducing schizophrenia-like symptoms. 3-month-old C57BL/6J mice received daily injections of PCP (20 mg/kg, i.p.) or saline for one week. PCP-injected mice produced schizophrenia-like behaviours including impaired spatial short-term memory assessed by the Y-maze task and sensorimotor gating deficits in a prepulse inhibition task. Simultaneously, chronic PCP administration induced astrocyte and microglial activation in both the cortex and hippocampus. Additionally, the proinflammatory cytokine interleukin-1β was significantly up-regulated in PCP administrated mice. Furthermore, PCP treatment decreased ratio of the phospho-Ser9 epitope of glycogen synthase kinase-3β (GSK3β) over total GSK3β, which is indicative of increased GSK3β activity. These data demonstrate that chronic PCP in mouse produces inflammatory responses and GSK3β activation.

• Authors: Shenghua Zhu, Hongxing Wang, Ruoyang Shi, Ruiguo Zhang, Junhui Wang, Lynda Kong, Yingxia Sun, Jue He, Jiming Kong, Jun-Feng Wang, Xin-Min Li
• Journal: Neurochemical research (Neurochem Res) Vol. 39 Issue 12 Pg. 2385-93 (Dec 2014) ISSN: 1573-6903 [Electronic] United States
• PMID: 25270429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3
• Phencyclidine

Topics

• Animals
• Enzyme Activation
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Inflammation (chemically induced)
• Mice
• Phencyclidine (toxicity)