PMID- 20826199
OWN - NLM
STAT- MEDLINE
DCOM- 20110202
LR  - 20161125
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 171
IP  - 1
DP  - 2010 Nov 24
TI  - Activation of phosphatidylinositol 3-kinase/Akt-mammalian target of Rapamycin 
      signaling pathway in the hippocampus is essential for the acquisition of 
      morphine-induced place preference in rats.
PG  - 134-43
LID - 10.1016/j.neuroscience.2010.08.064 [doi]
AB  - Hippocampus is a critical structure for the acquisition of morphine-induced 
      conditioned place preference (CPP), which is a usual learning paradigm for 
      assessing drug reward. However, the precise mechanisms remain largely unknown. 
      Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt, 
      mammalian target of Rapamycin (mTOR) and 70-kDa ribosomal S6 kinase (p70S6K), are 
      critical molecules implicated in learning and memory. Here, we tested the role of 
      PI3K/Akt-mTOR-p70S6K signaling pathway in morphine-induced CPP in the 
      hippocampus. Our results showed that the acquisition of morphine CPP increased 
      phosphorylation of Akt in the hippocampal CA3, but not in the nucleus accumbens 
      (NAc), the ventral tegmental area (VTA) or the CA1. Moreover, the phosphorylated 
      Akt exclusively expressed in the CA3 neurons. Likewise, levels of phosphorylated 
      mTOR and p70S6K were significantly enhanced in the CA3 following morphine CPP. 
      The alterations of these phosphorylated proteins are positively correlated with 
      the acquisition of morphine CPP. More importantly, microinjection of PI3K 
      inhibitor (LY294002) or mTOR inhibitor (Rapamycin) into the CA3 prevented the 
      acquisition of CPP and inhibited the activation of PI3K-Akt signaling pathway. In 
      addition, pre-infusion of beta-FNA (beta-funaltrexamine hydrochloride), a selective 
      irreversible mu opioid receptor antagonist, into CA3 significantly prevented the 
      acquisition of CPP and impaired Akt phosphorylation. All these results strongly 
      implied that the PI3K-Akt signaling pathway activated by mu opioid receptor in 
      hippocampal CA3 plays an important role in acquisition of morphine-induced CPP.
CI  - Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Cui, Yue
AU  - Cui Y
AD  - Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun 
      Yat-Sen University, 74 Zhongshan Road 2, Guangzhou, 510080, PR China.
FAU - Zhang, X Q
AU  - Zhang XQ
FAU - Cui, Y
AU  - Cui Y
FAU - Xin, W J
AU  - Xin WJ
FAU - Jing, J
AU  - Jing J
FAU - Liu, X G
AU  - Liu XG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100906
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Morpholines)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Narcotics)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 5S6W795CQM (Naltrexone)
RN  - 72782-05-9 (beta-funaltrexamine)
RN  - 76I7G6D29C (Morphine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Chromones/pharmacology
MH  - Conditioning, Operant/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hippocampus/*drug effects/enzymology
MH  - Male
MH  - Morphine/*pharmacology
MH  - Morpholines/pharmacology
MH  - Naltrexone/analogs & derivatives/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Narcotics/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphopyruvate Hydratase/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - Statistics as Topic
EDAT- 2010/09/10 06:00
MHDA- 2011/02/03 06:00
CRDT- 2010/09/10 06:00
PHST- 2010/07/01 00:00 [received]
PHST- 2010/08/25 00:00 [revised]
PHST- 2010/08/30 00:00 [accepted]
PHST- 2010/09/10 06:00 [entrez]
PHST- 2010/09/10 06:00 [pubmed]
PHST- 2011/02/03 06:00 [medline]
AID - S0306-4522(10)01214-5 [pii]
AID - 10.1016/j.neuroscience.2010.08.064 [doi]
PST - ppublish
SO  - Neuroscience. 2010 Nov 24;171(1):134-43. doi: 10.1016/j.neuroscience.2010.08.064. 
      Epub 2010 Sep 6.