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Behavioral Sensitivity and Ethanol Potentiation of the N ‐Methyl‐d‐Aspartate Receptor Antagonist MK‐801 in a Rat Line Selected for High Ethanol Sensitivity
Author(s) -
Toropainen M.,
Näkki R.,
Honkanen A.,
Rosenberg P. H.,
Laurie D. J.,
PeltoHuikko M.,
Koistinaho J.,
Eriksson C. J. P.,
Korpi E. R.
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb03820.x
Subject(s) - nmda receptor , dizocilpine , ethanol , stimulation , long term potentiation , chemistry , pharmacology , antagonist , receptor , medicine , neurochemical , endocrinology , receptor antagonist , glutamate receptor , alcohol , biology , biochemistry
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 impairment was studied in behavioral and neurochemical experiments. A noncompetitive antagonist of the NMDA receptor, dirocilpine mal‐eate (MK‐801; 0.2 mg/kg), impaired motor function in ANT rats, but not in AT rats, in a tilting plane test. The impairment was further potentiated by a dose (0.75 glkg) of ethanol, which alone was inactive. This effect was apparently not associated with the locomotor stimulation produced by MK‐801 (0.1 and 0.2 mg/kg), because stimulation did not differ between the rat lines. Locomotor stimulation was potentiated by the low ethanol dose in both rat lines. Ethanol treatment decreased the cerebellar and hippocampal cGMP concentrations both with and without MK‐801 pretreatment in both rat lines. In situ hybridization using oligonucleotide probes specific for NMDA receptor subunit mRNAs NR1 and NR2A, B, C, and D revealed no clear differences in brain regional expression between ANT and AT rats. These results indicate that the alcohol‐sensitive ANT rats are very sensitive to a low dose of ethanol in the presence of NMDA receptor antagonism, consistent with the hypothesis that this receptor system is involved in acute ethanol intoxication.