PMID- 16150934
OWN - NLM
STAT- MEDLINE
DCOM- 20060119
LR  - 20191210
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 68
IP  - 6
DP  - 2005 Dec
TI  - Long-lasting impairment of associative learning is correlated with a dysfunction 
      of N-methyl-D-aspartate-extracellular signaling-regulated kinase signaling in 
      mice after withdrawal from repeated administration of phencyclidine.
PG  - 1765-74
AB  - In humans, the administration of phencyclidine causes schizophrenic-like symptoms 
      that persist for several weeks after withdrawal from phencyclidine use. We 
      demonstrated here that mice pretreated with phencyclidine (10 mg/kg/day s.c. for 
      14 days) showed an enduring impairment of associative in a Pavlovian fear 
      conditioning 8 days after cessation of phencyclidine treatment. Extracellular 
      signaling-regulated kinase (ERK) was transiently activated in the amygdalae and 
      hippocampi of saline-treated mice after conditioning. In the 
      phencyclidine-treated mice, the basal level of ERK activation was elevated in the 
      hippocampus, whereas the activation was impaired in the amygdala and hippocampus 
      after conditioning. Exogenous N-methyl-D-aspartate (NMDA), glycine, and 
      spermidine-induced ERK activation was not observed in slices of hippocampus and 
      amygdala prepared from phencyclidine-treated mice. Repeated olanzapine (3 
      mg/kg/day p.o. for 7 days), but not haloperidol (1 mg/kg/day p.o. for 7 days), 
      treatment reversed the impairment of associative learning and of fear 
      conditioning-induced ERK activation in repeated phencyclidine-treated mice. Our 
      findings suggest an involvement of abnormal ERK signaling via NMDA receptors in 
      repeated phencyclidine treatment-induced cognitive dysfunction. Furthermore, our 
      phencyclidine-treated mice would be a useful model for studying the effect of 
      antipsychotics on cognitive dysfunction in schizophrenia.
FAU - Enomoto, Takeshi
AU  - Enomoto T
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, 65 Tsurum-cho, Showa-ku, Nagoya 466-8560, Japan.
FAU - Noda, Yukihiro
AU  - Noda Y
FAU - Mouri, Akihiro
AU  - Mouri A
FAU - Shin, Eun-Joo
AU  - Shin EJ
FAU - Wang, Dayong
AU  - Wang D
FAU - Murai, Rina
AU  - Murai R
FAU - Hotta, Kazuo
AU  - Hotta K
FAU - Furukawa, Hiroshi
AU  - Furukawa H
FAU - Nitta, Atsumi
AU  - Nitta A
FAU - Kim, Hyoung-Chun
AU  - Kim HC
FAU - Nabeshima, Toshitaka
AU  - Nabeshima T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050908
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - Amygdala/drug effects
MH  - Animals
MH  - Conditioning, Psychological
MH  - Extracellular Signal-Regulated MAP Kinases/analysis/*metabolism
MH  - Fear
MH  - Hippocampus/drug effects
MH  - Learning Disabilities/*chemically induced/drug therapy
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - N-Methylaspartate/*pharmacology
MH  - Phencyclidine/administration & dosage/*toxicity
MH  - *Substance Withdrawal Syndrome
EDAT- 2005/09/10 09:00
MHDA- 2006/01/20 09:00
CRDT- 2005/09/10 09:00
PHST- 2005/09/10 09:00 [pubmed]
PHST- 2006/01/20 09:00 [medline]
PHST- 2005/09/10 09:00 [entrez]
AID - mol.105.011304 [pii]
AID - 10.1124/mol.105.011304 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2005 Dec;68(6):1765-74. doi: 10.1124/mol.105.011304. Epub 2005 Sep 
      8.