PMID- 18703114
OWN - NLM
STAT- MEDLINE
DCOM- 20090203
LR  - 20131121
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 444
IP  - 1
DP  - 2008 Oct 17
TI  - A pharmacological MRI assessment of dizocilpine (MK-801) in the 3-nitroproprionic 
      acid-lesioned rat.
PG  - 42-7
LID - 10.1016/j.neulet.2008.07.090 [doi]
AB  - The NMDA-antagonist dizocilpine (MK-801) is known to have dissociative, 
      neurotoxic and neuroprotective properties. Although its neuroprotective 
      properties are well documented, at present only ex vivo autoradiography has 
      demonstrated its activity in lesioned brains. We report here the use of 
      pharmacological magnetic resonance imaging (phMRI) to visualise the neural 
      substrates of MK-801 in normal control rats and in animals that received systemic 
      3-nitroproprionic acid (3-NPA) 2 weeks earlier. In control animals, this 
      NMDA-antagonist resulted in activity in the hippocampus, retrospinal (RS) cortex, 
      anterior cingulate and the medial prefrontal cortex (MPFC). Activity in the MPFC 
      has been associated with the dissociative properties of this agent and has been 
      suggested to be the neurological substrate of positive psychotic symptoms, 
      whereas RS and hippocampus have been the main sites of neurotoxic actions of 
      MK-801. In contrast, in animals with 3-NPA-lesions affecting the striatum, no 
      activity in the MPFC was observed, but a positive BOLD signal in the striatum was 
      apparent. Lesioned animals injected with saline did not show this pattern of 
      activity indicating that it is not merely an artefact of the ongoing 
      neurodegeneration. This striatal activity could therefore be a site of 
      MK-801-mediated neuroprotection. phMRI therefore sheds further light on the in 
      vivo activity of MK-801 which, in turn, may allow us to more fully understand the 
      different actions of NMDA-antagonists.
FAU - Roberts, Toby J
AU  - Roberts TJ
AD  - Neuroimaging Research Group, Department of Clinical Neuroscience, Institute of 
      Psychiatry, King's College London, London SE5 8AF, UK.
FAU - Williams, Steven C R
AU  - Williams SC
FAU - Modo, Michel
AU  - Modo M
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080805
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Boronic Acids)
RN  - 0 (Neuroprotective Agents)
RN  - 13331-27-6 (3-nitrobenzeneboronic acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Blood Pressure/drug effects
MH  - Boronic Acids/*toxicity
MH  - Brain Mapping
MH  - *Corpus Striatum/drug effects/injuries/pathology
MH  - Dizocilpine Maleate/*pharmacology
MH  - Heart Rate/drug effects
MH  - Magnetic Resonance Imaging/*methods
MH  - Male
MH  - Motor Activity/drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Stereotyped Behavior/drug effects
EDAT- 2008/08/16 09:00
MHDA- 2009/02/04 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/06/04 00:00 [received]
PHST- 2008/07/27 00:00 [revised]
PHST- 2008/07/28 00:00 [accepted]
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2009/02/04 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
AID - S0304-3940(08)01069-0 [pii]
AID - 10.1016/j.neulet.2008.07.090 [doi]
PST - ppublish
SO  - Neurosci Lett. 2008 Oct 17;444(1):42-7. doi: 10.1016/j.neulet.2008.07.090. Epub 
      2008 Aug 5.