PMID- 10591601
OWN - NLM
STAT- MEDLINE
DCOM- 19991230
LR  - 20131121
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 23
IP  - 11
DP  - 1999 Nov
TI  - Ethanol pretreatment enhances NMDA excitotoxicity in biogenic amine neurons: 
      protection by brain derived neurotrophic factor.
PG  - 1834-42
AB  - BACKGROUND: Biogenic amine neurons are involved in a number of mental diseases 
      including addiction and alcohol dependence. Because chronic ethanol is known to 
      cause supersensitivity to NMDA excitotoxicity in cortical neurons, this study 
      sought to determine the effect of ethanol treatment on biogenic amine neurons. 
      METHODS: To determine if ethanol exposure alters the vitality of biogenic amine 
      neurons, cultures were prepared from E14 rat brain. After 24 hr in culture, cells 
      were divided into control or ethanol (100 mM) treatment groups, cultured an 
      additional 48 hr, and then half of them exposed to NMDA for 25 min. The NMDA was 
      then removed and cells cultured in fresh media for an additional 24 hr to allow 
      for excitotoxic delayed neuronal death. Cultures were then stained with 
      antibodies to 5-hydroxytryptamine or tyrosine hydroxylase to identify serotonin 
      and dopamine neurons, respectively. Cultures were analyzed for cell number and 
      neuronal morphology. RESULTS: Ethanol treatment alone had no effect on biogenic 
      amine cell number, soma area, number of neurites, or terminal segments, although 
      the field area of dopamine neurons was decreased. Treatment with 30 microM NMDA 
      had no effect on controls, but significantly decreased dopamine neurons in 
      ethanol-treated cultures as well as reduced soma area, field area, number of 
      neurites and number of terminal segments. Treatment with higher concentrations of 
      NMDA reduced dopamine and serotonin neurons in both controls and ethanol-treated 
      groups, and ethanol treatment significantly enhanced NMDA excitotoxic effects. 
      Treatment with Brain Derived Neurotrophic Factor (BDNF) prevented ethanol 
      sensitization to NMDA excitotoxicity. CONCLUSIONS: These studies suggest that 
      ethanol treatment sensitizes biogenic amine neurons to excitotoxic insults. 
      Ethanol sensitization of biogenic amine neurons to insults could contribute to 
      the development of mental disease.
FAU - Crews, F T
AU  - Crews FT
AD  - Center for Alcohol Studies, University of North Carolina, Chapel Hill 27599-7178, 
      USA. ftcrews@med.unc.edu
FAU - Waage, H G
AU  - Waage HG
FAU - Wilkie, M B
AU  - Wilkie MB
FAU - Lauder, J M
AU  - Lauder JM
LA  - eng
PT  - Journal Article
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 (Biogenic Amines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 3K9958V90M (Ethanol)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Biogenic Amines/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*pharmacology
MH  - Ethanol/*pharmacology
MH  - Excitatory Amino Acid Agonists/*pharmacology
MH  - Female
MH  - N-Methylaspartate/drug effects/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1999/12/11 00:00
MHDA- 1999/12/11 00:01
CRDT- 1999/12/11 00:00
PHST- 1999/12/11 00:00 [pubmed]
PHST- 1999/12/11 00:01 [medline]
PHST- 1999/12/11 00:00 [entrez]
AID - 00000374-199911000-00017 [pii]
PST - ppublish
SO  - Alcohol Clin Exp Res. 1999 Nov;23(11):1834-42.