GENETIC-DETERMINANTS OF MORPHINE ACTIVITY AND THERMAL RESPONSES IN 15INBRED MOUSE STRAINS

Mice from 15 standard inbred strains were tested for sensitivity to tw o effects or acute morphine administration, open-field activity, and b ody temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, IP. La rge strain differences were consistently observed, indicating a substa ntial degree of genetic determination of these traits. For morphine-in duced activity, some strains were markedly insensitive to all doses (e .g., C3H/He, CE), while others showed increases and some decreases at the same morphine dose. For thermal responses, one strain was insensit ive to all doses employed (C3H/He), while others showed marked hypothe rmia and some hyperthermia at the same dose. Although strains differed in brain morphine concentrations at time of behavioral testing, pharm acokinetic differences were unrelated to both measures of morphine sen sitivity. Correlations among strain means (estimates of genetic correl ations) were rather high across doses within each measure, indicating that strain differences to a given effect of morphine were rather stab le across doses. This suggests substantial commonality in genetically mediated mechanisms across the dose range used for activity, and also for thermal responses. In contrast, genetic correlations between activ ity and thermal responses were not significant at any dose, indicating that these two traits are largely genetically independent. (C) 1998 E lsevier Science Inc.