PMID- 24257811
OWN - NLM
STAT- MEDLINE
DCOM- 20141124
LR  - 20240321
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Print)
IS  - 0269-8811 (Linking)
VI  - 28
IP  - 4
DP  - 2014 Apr
TI  - Reviewing the ketamine model for schizophrenia.
PG  - 287-302
LID - 10.1177/0269881113512909 [doi]
AB  - The observation that antagonists of the N-methyl-D-aspartate receptor (NMDAR), 
      such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute 
      schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic 
      dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis 
      can explain negative and cognitive symptoms of schizophrenia better than the 
      dopamine hypothesis, and has the potential to explain dopamine dysfunction 
      itself. The pharmacological and psychomimetic effects of ketamine, which is safer 
      for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a 
      variety of receptors, but principally acts at the NMDAR, and convergent genetic 
      and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, 
      NMDAR hypofunction can explain connectional and oscillatory abnormalities in 
      schizophrenia in terms of both weakened excitation of inhibitory gamma-aminobutyric 
      acidergic (GABAergic) interneurons that synchronize cortical networks and 
      disinhibition of principal cells. Individuals with prenatal NMDAR aberrations 
      might experience the onset of schizophrenia towards the completion of synaptic 
      pruning in adolescence, when network connectivity drops below a critical value. 
      We conclude that ketamine challenge is useful for studying the positive, 
      negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of 
      onset, functional dysconnectivity, and abnormal cortical oscillations observed in 
      acute schizophrenia.
FAU - Frohlich, Joel
AU  - Frohlich J
AD  - 1UCLA Center for Autism Research and Treatment (CART), University of California, 
      Los Angeles, CA, USA.
FAU - Van Horn, John D
AU  - Van Horn JD
LA  - eng
GR  - P41 EB015922/EB/NIBIB NIH HHS/United States
GR  - U54 EB005149/EB/NIBIB NIH HHS/United States
GR  - R41 NS081792/NS/NINDS NIH HHS/United States
GR  - R41NS081792/NS/NINDS NIH HHS/United States
GR  - 2U54EB005149/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20131120
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 690G0D6V8H (Ketamine)
RN  - J1DOI7UV76 (Phencyclidine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Age of Onset
MH  - Animals
MH  - Dopamine/metabolism
MH  - Humans
MH  - Ketamine/*pharmacology
MH  - Phencyclidine/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Schizophrenia/genetics/*physiopathology
MH  - Schizophrenic Psychology
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC4133098
MID - NIHMS611802
OTO - NOTNLM
OT  - Ketamine
OT  - N-methyl-D-aspartate receptor
OT  - glutamate
OT  - schizophrenia
COIS- Conflict of interest J.D.V.H. receives partial support as a consultant through an 
      NIH STTR sub-award from Kitware, Inc., a medical imaging processing and 
      visualization company based in Clifton Park, NY and Carrboro, North Carolina, 
      USA. This article does not advocate for or against the products of this company 
      and is not intended to represent the views or mission of Kitware, Inc. The 
      authors declare no other potential conflicts of interest.
EDAT- 2013/11/22 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/08/14
CRDT- 2013/11/22 06:00
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/08/14 00:00 [pmc-release]
AID - 0269881113512909 [pii]
AID - 10.1177/0269881113512909 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2014 Apr;28(4):287-302. doi: 10.1177/0269881113512909. Epub 
      2013 Nov 20.