PMID- 23611177
OWN - NLM
STAT- MEDLINE
DCOM- 20141009
LR  - 20211203
IS  - 1488-2434 (Electronic)
IS  - 1180-4882 (Print)
IS  - 1180-4882 (Linking)
VI  - 38
IP  - 5
DP  - 2013 Sep
TI  - Glycine site N-methyl-D-aspartate receptor antagonist 7-CTKA produces rapid 
      antidepressant-like effects in male rats.
PG  - 306-16
LID - 10.1503/jpn.120228 [doi]
AB  - BACKGROUND: Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists exert 
      fast-acting antidepressant effects, providing a promising way to develop a new 
      classification of antidepressant that targets the glutamatergic system. In the 
      present study, we examined the potential antidepressant action of 
      7-chlorokynurenic acid (7-CTKA), a glycine recognition site NMDA receptor 
      antagonist, in a series of behavioural models of depression and determined the 
      molecular mechanisms that underlie the behavioural actions of 7-CTKA. METHODS: We 
      administered the forced swim test, novelty-suppressed feeding test, learned 
      helplessness paradigm and chronic mild stress (CMS) paradigm in male rats to 
      evaluate the possible rapid antidepressant-like actions of 7-CTKA. In addition, 
      we assessed phospho-glycogen synthase kinase-3beta (p-GSK3beta) level, mammalian target 
      of rapamycin (mTOR) function, and postsynaptic protein expression in the medial 
      prefrontal cortex (mPFC) and hippocampus. RESULTS: Acute 7-CTKA administration 
      produced rapid antidepressant-like actions in several behavioural tests. It 
      increased p-GSK3beta, enhanced mTOR function and increased postsynaptic protein 
      levels in the mPFC. Activation of GSK3beta by LY294002 completely blocked the 
      antidepressant-like effects of 7-CTKA. Moreover, 7-CTKA did not produce rewarding 
      properties or abuse potential. LIMITATIONS: It is possible that 7-CTKA modulates 
      glutamatergic transmission, thereby causing enduring alterations of GSK3beta and 
      mTOR signalling, although we did not provide direct evidence to support this 
      possibility. Thus, the therapeutic involvement of synaptic adaptions engaged by 
      7-CTKA requires further study. CONCLUSION: Our findings demonstrate that acute 
      7-CTKA administration produced rapid antidepressant-like effects, indicating that 
      the behavioural response to 7-CTKA is mediated by GSK3beta and mTOR signalling 
      function in the mPFC.
FAU - Zhu, Wei-Li
AU  - Zhu WL
AD  - National Institute on Drug Dependence, Peking University, Beijing, China.
FAU - Wang, Shen-Jun
AU  - Wang SJ
FAU - Liu, Meng-Meng
AU  - Liu MM
FAU - Shi, Hai-Shui
AU  - Shi HS
FAU - Zhang, Ruo-Xi
AU  - Zhang RX
FAU - Liu, Jian-Feng
AU  - Liu JF
FAU - Ding, Zeng-Bo
AU  - Ding ZB
FAU - Lu, Lin
AU  - Lu L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Psychiatry Neurosci
JT  - Journal of psychiatry & neuroscience : JPN
JID - 9107859
RN  - 0 (Antidepressive Agents)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Activators)
RN  - 0 (Morpholines)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - H030S2S85J (Kynurenic Acid)
RN  - S7936QON2K (7-chlorokynurenic acid)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Choice Behavior/drug effects
MH  - Chromones/administration & dosage/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activators/pharmacology
MH  - Feeding Behavior/drug effects
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Helplessness, Learned
MH  - Hippocampus/drug effects/metabolism
MH  - Immobility Response, Tonic/drug effects
MH  - Kynurenic Acid/*analogs & derivatives/antagonists & inhibitors/pharmacology
MH  - Male
MH  - Microinjections
MH  - Morpholines/administration & dosage/pharmacology
MH  - Nerve Tissue Proteins/metabolism
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Stress, Psychological/psychology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3756114
EDAT- 2013/04/25 06:00
MHDA- 2014/10/10 06:00
PMCR- 2013/09/01
CRDT- 2013/04/25 06:00
PHST- 2013/04/25 06:00 [entrez]
PHST- 2013/04/25 06:00 [pubmed]
PHST- 2014/10/10 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1503/jpn.120228 [pii]
AID - pg306 [pii]
AID - 10.1503/jpn.120228 [doi]
PST - ppublish
SO  - J Psychiatry Neurosci. 2013 Sep;38(5):306-16. doi: 10.1503/jpn.120228.