PMID- 15647751
OWN - NLM
STAT- MEDLINE
DCOM- 20050421
LR  - 20150311
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 30
IP  - 3
DP  - 2005 Mar
TI  - Selective cognitive impairments associated with NMDA receptor blockade in humans.
PG  - 633-9
AB  - Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) may be involved in the 
      pathophysiology of schizophrenia. NMDAR antagonists like ketamine induce 
      schizophrenia-like features in humans. In rodent studies, NMDAR antagonism 
      impairs learning by disrupting long-term potentiation (LTP) in the hippocampus. 
      This study investigated the effects of ketamine on spatial learning (acquisition) 
      vs retrieval in a virtual Morris water task in humans. Verbal fluency, working 
      memory, and learning and memory of verbal information were also assessed. Healthy 
      human subjects participated in this double-blinded, placebo-controlled study. On 
      two separate occasions, ketamine/placebo was administered and cognitive tasks 
      were assessed in association with behavioral ratings. Ketamine impaired learning 
      of spatial and verbal information but retrieval of information learned prior to 
      drug administration was preserved. Schizophrenia-like symptoms were significantly 
      related to spatial and verbal learning performance. Ketamine did not 
      significantly impair attention, verbal fluency, or verbal working memory task 
      performance. Spatial working memory was slightly impaired. In conclusion, these 
      results provide evidence for ketamine's differential impairment of verbal and 
      spatial learning vs retrieval. By using the Morris water task, which is 
      hippocampal-dependent, this study helps bridge the gap between nonhuman animal 
      and human NMDAR antagonism research. Impaired cognition is a core feature of 
      schizophrenia. A better understanding of NMDA antagonism, its physiological and 
      cognitive consequences, may provide improved models of psychosis and cognitive 
      therapeutics.
FAU - Rowland, Laura M
AU  - Rowland LM
AD  - Maryland Psychiatric Research Center, University of Maryland School of Medicine, 
      Baltimore, MD 21228, USA. lrowland@mprc.umaryland.edu
FAU - Astur, Robert S
AU  - Astur RS
FAU - Jung, Rex E
AU  - Jung RE
FAU - Bustillo, Juan R
AU  - Bustillo JR
FAU - Lauriello, John
AU  - Lauriello J
FAU - Yeo, Ronald A
AU  - Yeo RA
LA  - eng
GR  - NIH NS07375/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Placebos)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Cognition Disorders/*physiopathology
MH  - Double-Blind Method
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Humans
MH  - Ketamine/pharmacology
MH  - Learning/drug effects/physiology
MH  - Memory/drug effects/physiology
MH  - Placebos
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Reference Values
MH  - Space Perception/drug effects/physiology
MH  - Swimming
EDAT- 2005/01/14 09:00
MHDA- 2005/04/22 09:00
CRDT- 2005/01/14 09:00
PHST- 2005/01/14 09:00 [pubmed]
PHST- 2005/04/22 09:00 [medline]
PHST- 2005/01/14 09:00 [entrez]
AID - 1300642 [pii]
AID - 10.1038/sj.npp.1300642 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2005 Mar;30(3):633-9. doi: 10.1038/sj.npp.1300642.