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Effects of ethanol and temperature on NMDA receptor function in different mouse genotypes
W Musleh1, S Alvarez, M Baudry
1Neuroscience Program, University of Southern California, Los Angeles, USA.
Alcoholism, Clinical and Experimental Research
|October 1, 1996
Summary
Temperature significantly impacts how NMDA receptors respond to ethanol across different mouse genotypes. Lower temperatures increase ethanol
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Ethanol's effects on behavior are influenced by body temperature.
- NMDA receptors are crucial for synaptic plasticity and are targets for ethanol.
Purpose of the Study:
- To investigate if temperature-dependent changes in NMDA receptor sensitivity to ethanol mediate behavioral responses.
- To determine genotypic differences in NMDA receptor sensitivity to ethanol at varying temperatures.
Main Methods:
- Examined NMDA receptor-mediated synaptic potentials in hippocampal slices from three mouse genotypes (C57, LS, SS) at 30°C and 35°C.
- Assessed ethanol's effect on glutamate-stimulated [3H]MK-801 binding in brain membrane preparations across genotypes and temperatures.
Main Results:
- Ethanol decreased NMDA receptor-mediated EPSP amplitude and area in all genotypes, with greater effects at 30°C in C57 mice.
- Genotype sensitivity order varied with temperature: C57=LS>SS at 35°C and C57>LS=SS at 30°C for EPSPs.
- Ethanol inhibited [3H]MK-801 binding more at 30°C than 35°C across all genotypes, with varying genotype sensitivity.
- Temperature significantly influenced NMDA receptor sensitivity to ethanol, affecting genotype-specific responses.
Conclusions:
- Temperature is a critical factor modulating NMDA receptor sensitivity to ethanol.
- Temperature-induced changes in NMDA receptor sensitivity may influence ethanol's behavioral effects, particularly in LS mice.
- Findings highlight the complex interplay between temperature, genotype, and ethanol neurotoxicity.