PMID- 18571865
OWN - NLM
STAT- MEDLINE
DCOM- 20090409
LR  - 20131121
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 158
IP  - 1
DP  - 2009 Jan 12
TI  - N-methyl-D-aspartate receptor subunit dysfunction at hippocampal glutamatergic 
      synapses in an animal model of attention-deficit/hyperactivity disorder.
PG  - 353-64
LID - 10.1016/j.neuroscience.2008.05.016 [doi]
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common 
      neurobehavioural disorder among children. ADHD children are hyperactive, 
      impulsive and have problems with sustained attention. These cardinal features are 
      also present in the best validated animal model of ADHD, the spontaneously 
      hypertensive rat (SHR), which is derived from the Wistar Kyoto rat (WKY). Current 
      theories of ADHD relate symptom development to factors that alter learning. 
      N-methyl-D-aspartate receptor (NMDAR) dependent long term changes in synaptic 
      efficacy in the mammalian CNS are thought to represent underlying cellular 
      mechanisms for some forms of learning. We therefore hypothesized that synaptic 
      abnormality in excitatory, glutamatergic synaptic transmission might contribute 
      to the altered behavior in SHRs. We studied physiological and anatomical aspects 
      of hippocampal CA3-to-CA1 synapses in age-matched SHR and WKY (controls). 
      Electrophysiological analysis of these synapses showed reduced synaptic 
      transmission (reduced field excitatory postsynaptic potential for a defined fiber 
      volley size) in SHR, whereas short-term forms of synaptic plasticity, like 
      paired-pulse facilitation, frequency facilitation, and delayed response 
      enhancement were comparable in the two genotypes, and long-term potentiation 
      (LTP) of synaptic transmission was of similar magnitude. However, LTP in SHR was 
      significantly reduced (by 50%) by the NR2B specific blocker CP-101,606 (10 
      microM), whereas the blocker had no effect on LTP magnitude in the control rats. 
      This indicates that the SHR has a functional predominance of NR2B, a feature 
      characteristic of early developmental stages in these synapses. Quantitative 
      immunofluorescence and electron microscopic postembedding immunogold 
      cytochemistry of the three major NMDAR subunits (NR1, NR2A; and NR2B) in stratum 
      radiatum spine synapses revealed no differences between SHR and WKY. The results 
      indicate that functional impairments in glutamatergic synaptic transmission may 
      be one of the underlying mechanisms leading to the abnormal behavior in SHR, and 
      possibly in human ADHD.
FAU - Jensen, V
AU  - Jensen V
AD  - Molecular Neurobiology Research Group, Institute of Basic Medical Sciences, 
      University of Oslo, Oslo, Norway.
FAU - Rinholm, J E
AU  - Rinholm JE
FAU - Johansen, T J
AU  - Johansen TJ
FAU - Medin, T
AU  - Medin T
FAU - Storm-Mathisen, J
AU  - Storm-Mathisen J
FAU - Sagvolden, T
AU  - Sagvolden T
FAU - Hvalby, O
AU  - Hvalby O
FAU - Bergersen, L H
AU  - Bergersen LH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080521
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Attention Deficit Disorder with 
      Hyperactivity/genetics/*metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Excitatory Postsynaptic Potentials/physiology
MH  - Genotype
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/*metabolism/physiopathology/ultrastructure
MH  - Long-Term Potentiation/genetics/physiology
MH  - Male
MH  - Protein Subunits/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/genetics/*metabolism
MH  - Species Specificity
MH  - Synapses/*metabolism/ultrastructure
MH  - Synaptic Transmission/*genetics
EDAT- 2008/06/24 09:00
MHDA- 2009/04/10 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/02/15 00:00 [received]
PHST- 2008/05/13 00:00 [revised]
PHST- 2008/05/15 00:00 [accepted]
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2009/04/10 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - S0306-4522(08)00767-7 [pii]
AID - 10.1016/j.neuroscience.2008.05.016 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Jan 12;158(1):353-64. doi: 10.1016/j.neuroscience.2008.05.016. 
      Epub 2008 May 21.