QUANTITATIVE-TRAIT-LOCI (QTL) APPLICATIONS TO SUBSTANCES OF ABUSE - PHYSICAL-DEPENDENCE STUDIES WITH NITROUS-OXIDE AND ETHANOL IN BXD MICE

Recombinant inbred (RI) mouse strains were developed primarily as a to ol to detect and provisionally map major gene loci-those with effects large enough to cause a bimodal distribution in the trait of interest. This implied that progress toward gene mapping was possible only for gene loci accounting for at least half of the genetic variance. More r ecently, QTL (quantitative trait loci) approaches have been advanced t hat do not require bimodal distributions and are thus applicable to a much wider range of phenotypes. They offer the prospect of meaningful progress toward detecting and mapping minor as well as major gene loci affecting any trait of interest, provided there is a significant degr ee of genetic determination among the RI strains. This paper presents a review of RI gene mapping efforts concerning phenotypes related to d rug abuse and presents new data for studies now in progress for nitrou s oxide and acute ethanol withdrawal intensity. These two studies exem plify several strengths and limitations of the RI QTL approach.