BEHAVIORAL SENSITIVITY AND ETHANOL POTENTIATION OF THE N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST MK-801 IN A RAT LINE SELECTED FOR HIGH ETHANOL SENSITIVITY

The role of the N-methyl-D-aspartate (NMDA) receptors in differential ethanol sensitivity of the alcohol-insensitive [alcohol-tolerant (AT)] and alcohol-sensitive [alcohol-nontolerant (ANT)] rat lines selected for low and high sensitivity to ethanol-induced (2 g/kg) motor impairm ent was studied in behavioral and neurochemical experiments. A noncomp etitive antagonist of the NMDA receptor, dizocilpine maleate (MK-801; 0.2 mg/kg), impaired motor function in ANT rats, but not in AT rats, i n a tilting plane test. The impairment was further potentiated by a do se (0.75 g/kg) of ethanol, which alone was inactive. This effect was a pparently not associated with the locomotor stimulation produced by MK -801 (0.1 and 0.2 mg/kg), because stimulation did not differ between t he rat lines. Locomotor stimulation was potentiated by the low ethanol dose in both rat lines. Ethanol treat ment decreased the cerebellar a nd hippocampal cGMP concentrations both with and without MK-801 pretre atment in both rat lines. In situ hybridization using oligonucleotide probes specific for NMDA receptor subunit mRNAs NR1 and NR2A, B, C, an d D revealed no clear differences in brain regional expression between ANT and AT rats. These results indicate that the alcohol-sensitive AN T rats are very sensitive to a low dose of ethanol in the presence of NMDA receptor antagonism, consistent with the hypothesis that this rec eptor system is involved in acute ethanol intoxication.