The C57BL/6, DBA/2, and recombinant inbred (RI) strains derived from them (BxD RIs) are the most frequently studied mouse strains with regard to genetic regulation of voluntary ethanol consumption (YEC). We have studied VEC in an alternate genetic model provided by the LSxSS RIs. These RI strains exhibit phenotypic extremes in VEC comparable to the C57BL/6 and DBA/2 mice and genotype-dependent sex differences in drinking behavior. A correlational analysis between various ethanol-related behaviors suggests genetic independence of VEC from high-dose neurosensitivity (sleep time), acute ethanol tolerance, hypothermia, and low-dose locomotor activity. A search for quantitative trait loci identified a number of putative quantitative trait loci (QTL), three of which are identical to those previously reported for 10% ethanol drinking in the BxD RIs. We also find a significant correlation between low-affinity neurotensin receptor densities (NTRL) in the frontal cortex and VEC, and more common QTL between these two phenotypes than expected by chance. This suggests a role for frontal cortex NTRL in regulating voluntary ethanol intake.
Different densities of brain NMDARs are unlikely to account for the differential activation of LSXSS RI mice by MK-801. Additionally, in the RI mice either separate sets of genes regulate low dose MK-801- and ethanol-induced locomotor responses or the overlapping subset of genes controlling these two behaviors is small (< or =10%).
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