PMID- 10762370
OWN - NLM
STAT- MEDLINE
DCOM- 20000621
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 12
IP  - 4
DP  - 2000 Apr
TI  - Bilateral blockade of NMDA receptors in anterior thalamus by dizocilpine (MK-801) 
      injures pyramidal neurons in rat retrosplenial cortex.
PG  - 1420-30
AB  - Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine, 
      phencyclidine (PCP) and dizocilpine (MK-801), produce psychosis in people. In 
      rodents they produce cytoplasmic vacuoles in injured retrosplenial cortical 
      neurons that express HSP70 heat shock protein. This study examined possible 
      circuits and receptors that mediate this neuronal injury. Bilateral, but not 
      unilateral, injection of dizocilpine (5, 10, 15, 20 microg/microL per side) into 
      the anterior thalamus induced HSP70 protein in pyramidal neurons in deep layer 
      III of rat retrosplenial cortex 24 h later. In contrast, bilateral dizocilpine 
      injections (5, 10, 15, 20 microg/microL per side) into the retrosplenial cortex 
      or into the diagonal band of Broca did not induce HSP70. Bilateral injections of 
      muscimol (0.1, 1, 10 microg/microL per side), a GABAA (gamma-aminobutyric acid) 
      agonist, into the anterior thalamus blocked HSP70 induction in the retrosplenial 
      cortex produced by systemic dizocilpine (1 mg/kg). Bilateral thalamic injections 
      of baclofen (0.1, 1, 10 microg/microL per side), a GABAB agonist, were 
      ineffective. Anterograde tracer studies confirmed that neurons in the anterior 
      thalamus project to superficial layer III of the retrosplenial cortex where the 
      dendrites of HSP70-immunostained neurons in deep layer III reside. Bilateral 
      blockade of NMDA receptors on GABA neurons in the reticular nuclei of the 
      thalamus is proposed to decrease GABA neuronal firing, decrease GABA release and 
      decrease activation of GABAA receptors. This activates thalamic projection 
      neurons that damage retrosplenial cortical neurons presumably via unblocked 
      cortical glutamate alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) 
      and kainate receptors. The increases of blood flow that occur in the thalamus and 
      retrosplenial cortex of people that have psychosis produced by NMDA antagonists 
      could be related to thalamic excitation of the retrosplenial cortex produced by 
      these drugs.
FAU - Tomitaka, S
AU  - Tomitaka S
AD  - Departments of Neurology, University of California at San Francisco, San 
      Francisco, CA 94121, USA.
FAU - Tomitaka, M
AU  - Tomitaka M
FAU - Tolliver, B K
AU  - Tolliver BK
FAU - Sharp, F R
AU  - Sharp FR
LA  - eng
GR  - NS28167/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (GABA Agonists)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Phytohemagglutinins)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (leukoagglutinins, plants)
RN  - 2763-96-4 (Muscimol)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - H789N3FKE8 (Baclofen)
SB  - IM
MH  - Animals
MH  - Anterior Thalamic Nuclei/*cytology
MH  - Baclofen/pharmacology
MH  - Dizocilpine Maleate/*pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Female
MH  - GABA Agonists/pharmacology
MH  - Glutamic Acid/physiology
MH  - Gyrus Cinguli/*cytology
MH  - HSP70 Heat-Shock Proteins/analysis/biosynthesis
MH  - Muscimol/pharmacology
MH  - Nerve Degeneration/chemically induced/metabolism
MH  - Neural Pathways
MH  - Phytohemagglutinins
MH  - Pyramidal Cells/chemistry/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/physiology
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
MH  - Schizophrenia/physiopathology
MH  - gamma-Aminobutyric Acid/physiology
EDAT- 2000/04/13 09:00
MHDA- 2000/06/24 11:00
CRDT- 2000/04/13 09:00
PHST- 2000/04/13 09:00 [pubmed]
PHST- 2000/06/24 11:00 [medline]
PHST- 2000/04/13 09:00 [entrez]
AID - ejn018 [pii]
AID - 10.1046/j.1460-9568.2000.00018.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2000 Apr;12(4):1420-30. doi: 10.1046/j.1460-9568.2000.00018.x.