[3H]MK-801 binding in various brain regions of rat lines selected for differential alcohol sensitivity

Abstract

N-Methyl-D-aspartate (NMDA) receptors are sensitive to ethanol at concentrations relevant to intoxication. To ascertain possible involvement of NMDA receptors in differential ethanol sensitivity between alcohol-sensitive ANT (alcohol-nontolerant) and alcohol-insensitive AT (alcohol-tolerant) rat lines, characterization of a noncompetitive NMDA antagonist [3H]MK-801 binding to brain membranes was carried out. Saturation analyses of [3H]MK-801 binding to cerebrocortical, hippocampal, and cerebellar synaptosomal membranes revealed no statistically significant differences in either the affinity constant (Kd) or binding site density (Bmax) between the rat lines. Autoradiographic analysis of [3H]MK-801 binding to ANT and AT brain sections revealed a regionally heterogenous distribution of binding, without any detectable differences between the AT and ANT sections whether these were prepared from the brains of acutely ethanol-treated or nontreated animals. Glutamate, glycine, or the two in combination greatly increased [3H]MK-801 binding to brain membranes. In extensively washed crude cerebrocortical membranes, the maximal effect (Emax), but not potency (EC50) of glycine to increase [3H]MK-801 was slightly greater (p < 0.01) in the ANT than AT rats. The effects of glutamate or glutamate in the presence of saturating concentration of glycine (30 microM) were not significantly different between the two lines. Association parameters (t1/2 and Beq values) of [3H]MK-801 to its cortical binding sites were also similar. These results do not indicate any clear qualitative difference in [3H]MK-801 binding to NMDA receptors or in its modulation by glutamate and glycine between the ANT and AT rat lines.