Different levels of [3H]MK-801 binding in long-sleep and short-sleep lines of mice.

The long-sleep (LS) and short-sleep (SS) lines of mice were selectively bred for differential sensitivity to the hypnotic effects of ethanol. Several studies suggest that excitatory amino acid receptor systems are involved in these genetically determined differences in sensitivity to ethanol. The experiments described in this article examine further the potential role of NMDA excitatory amino acid receptors in genetically determined differences in hypnotic sensitivity to ethanol by measuring [3H]MK-801 binding in eight brain regions of LS and SS lines of mice. Significantly greater levels of binding were found in SS hippocampus and striatum. Binding levels in the remaining brain regions revealed no significant between-line differences. Affinity differences between regions were seen but no between-line differences in affinity were found in any brain region. These findings lend support to the hypothesis that differences in NMDA receptor systems are part of the genetically determined biochemistry that produces differential hypnotic sensitivity to ethanol in LS and SS mice.