PMID- 11141032
OWN - NLM
STAT- MEDLINE
DCOM- 20010315
LR  - 20131121
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 24
IP  - 12
DP  - 2000 Dec
TI  - N-methyl-D-aspartate receptor responses are differentially modulated by 
      noncompetitive receptor antagonists and ethanol in inbred long-sleep and 
      short-sleep mice: behavior and electrophysiology.
PG  - 1750-8
AB  - BACKGROUND: Short-sleep (SS) mice exhibit higher locomotor activity than do 
      long-sleep (LS) mice when injected with low doses of ethanol or the 
      noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 
      (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two 
      strains of LS X SS recombinant inbred (RI) mice also show differential activation 
      to ethanol and MK-801, but have similar numbers of NMDARs. Here we used inbred LS 
      (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs 
      and sensitivity to the stimulant effects of low doses of ethanol. METHODS: Open 
      field activity and spontaneous alternations were measured after saline or drug 
      injection. [3H]MK-801 binding parameters were determined in hippocampus, cortex, 
      striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic 
      potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices. 
      RESULTS: Systemic injection of either ethanol or MK-801 increased locomotor 
      activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR 
      antagonist 2-carboxypiperazin-4-yl-propyl-1-lphosphonic acid (+/- CPP) depressed 
      activity of ILS, but not ISS, mice. No strain differences were observed in 
      spontaneous alternations or in the number or affinity of NMDARs in the brain 
      regions examined. Likewise, the magnitudes of hippocampal NMDAR-mediated fEPSPs 
      were similar in ILS and ISS mice and were inhibited to the same extent by a 
      competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor 
      antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to 
      a greater extent in ISS, than in ILS, mice. CONCLUSIONS: Differential ethanol- 
      and MK-801-induced behavioral activation in ILS and ISS mice was not associated 
      with differences in NMDAR number. Nonetheless, pharmacological differences in 
      hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a 
      greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. 
      These differences, which may reflect differences in NMDAR subunit composition, 
      could underlie the differential responsiveness to low doses of ethanol in ILS and 
      ISS mice.
FAU - Hanania, T
AU  - Hanania T
AD  - Department of Pharmacology and Neuroscience Program, University of Colorado 
      Health Sciences Center, Denver, USA. taleen.hanania@uchsc.edu
FAU - Negri, C A
AU  - Negri CA
FAU - Dunwiddie, T V
AU  - Dunwiddie TV
FAU - Zahniser, N R
AU  - Zahniser NR
LA  - eng
GR  - NIAAA 03537/AA/NIAAA 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  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3K9958V90M (Ethanol)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Animals
MH  - Binding, Competitive/drug effects
MH  - Brain/*drug effects
MH  - Brain Mapping
MH  - Dizocilpine Maleate/*pharmacology
MH  - Ethanol/*pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Female
MH  - Hippocampus/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Radioligand Assay
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Recombination, Genetic
MH  - Sleep Stages/*drug effects/genetics
EDAT- 2001/01/05 11:00
MHDA- 2001/03/17 10:01
CRDT- 2001/01/05 11:00
PHST- 2001/01/05 11:00 [pubmed]
PHST- 2001/03/17 10:01 [medline]
PHST- 2001/01/05 11:00 [entrez]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2000 Dec;24(12):1750-8.