[H-3] MK-801 BINDING IN VARIOUS BRAIN-REGIONS OF RAT LINES SELECTED FOR DIFFERENTIAL ALCOHOL SENSITIVITY

N-Methyl-D-aspartate (NMDA) receptors are sensitive to ethanol at conc entrations relevant to intoxication. To ascertain possible involvement of NMDA receptors in differential ethanol sensitivity between alcohol -sensitive ANT (alcohol-nontolerant) and alcohol-insensitive AT (alcoh ol-tolerant) rat lines, characterization of a noncompetitive NMDA anta gonist [H-3]MK-801 binding to brain membranes was carried out. Saturat ion analyses of [H-3]Mg-801 binding to cerebrocortical, hippocampal, a nd cerebellar synaptosomal membranes revealed no statistically signifi cant differences in either the affinity constant (K-d) Or binding site density (B-max) between the rat lines. Autoradiographic analysis of [ H-3]MK-801 binding to ANT and AT brain sections revealed a regionally heterogenous distribution of binding, without any detectable differenc es between the AT and ANT sections whether these were prepared from th e brains of acutely ethanol-treated or nontreated animals. Glutamate, glycine, or the two in combination greatly increased [H-3]MK-801 bindi ng to brain membranes. In extensively washed crude cerebrocortical mem branes, the maximal effect (E(max), but not potency (EC(50)) of glycin e to increase [H-3]MK-801 was slightly greater (p < 0.01) in the ANT t han AT rats. The effects of glutamate or glutamate in the presence of saturating concentration of glycine (30 mu M) were not significantly d ifferent between the two lines. Association parameters (t(1/2) and B-e q values) of [H-3]MK-801 to its cortical binding sites were also simil ar. These results do not indicate any clear qualitative difference in [H-3]MK-801 binding to NMDA receptors or in its modulation by glutamat e and glycine between the ANT and AT rat lines.