Determination of the loci associated with morphine-induced physical dependence

It is well known that behavioral responses to drugs reflect genetic influence. The genetic influence on drug responses can be determined using inbred strains or recombinant inbred (RI) strains of mice. Recently, a growing body of evidence indicates that the genetic factors play a critical role in the modulation of pharmacological effects of morphine. In the present study, we investigated the determination of the chromosomes and loci associated with morphine-induced physical dependence using A/J, SM/J and their recombinant inbred (SMXA RI) strains of mice. In SMXA RI strains, the expression of naloxone (3 mg/kg, s.c.)-precipitated withdrawal signs after chronic morphine treatment was shown to be distributed unimodally. Quantitative trait loci (QTL) analysis of these data indicates that the morphine-induced physical dependence is mediated by several loci on the chromosomes. The present data suggest the possibility that the genes located on these loci may be dominantly implicated in the regulation of morphine-induced physical dependence.