ETHANOL SENSITIVITY OF BRAIN NMDA RECEPTORS IN MICE SELECTIVELY BRED FOR DIFFERENCES IN RESPONSE TO THE LOW-DOSE LOCOMOTOR STIMULANT EFFECTS OF ETHANOL

Brain NMDA receptor responses and their sensitivity to ethanol in vitro were determined in replicate lines of FAST and SLOW mice, selectively bred for differences in sensitivity to the locomotor stimulant effects of a low dose of ethanol. L-Glutamate-stimulated increases in the intracellular free calcium concentration (Ca-i) were determined in microsacs, a cell-free brain membrane preparation, isolated from hippocampus or cerebral cortex. Previous work showed that L-glutamate-stimulated increases in Ca-i in microsacs are mediated by activation of NMDA receptors. The concentration response far L-glutamate-stimulated increases in Ca-i did not differ between the lines in either hippocampal or cerebrocortical microsacs. Ethanol produced a concentration-dependent decrease in L-glutamate-stimulated increases in Ca-i in hippocampal and cerebrocortical microsacs from SLOW mice, but this effect of ethanol was reduced or absent in microsacs isolated from FAST mice. Resting Ca-i and the ability of a high ethanol concentration to increase resting Ca-i did not differ between the lines. These results suggest that differences in the sensitivity of brain NMDA receptors to the effects of ethanol determine, at least in part, differences in the locomotor stimulant effects of low doses of ethanol in FAST and SLOW mice. These differences are not due to ethanol effects on resting Ca-i.