Genetic dissociation of multiple morphine effects among C57BL/6J, DBA/2J and C3H/HeJ inbred mouse strains

The pattern of sensitivity of mice from three inbred strains were compared on measures of morphine-induced analgesia (hot plate), locomotor activity, hypothermia, Straub tail (muscular rigidity), antidiuresis and constipation. The DBA/2J strain emerged as the most sensitive strain for analgesia, retention of a water load (antidiuresis) and hypothermia. In addition, the DBA/2J mice had lower concentrations of morphine in the brain 30 min after injection and had the lowest Kd and the highest Bmax for naloxone as measured by in vitro receptor binding. In contrast, mice of the C57BL/6J strain were most sensitive when locomotor activity, Straub tail and constipation were measured. The C3H/HeJ mice were generally intermediate in their sensitivity to morphine. The observed strain differences indicate a rather high degree of genetic control for most of the effects studied, however, the low consistency of rank order among the three strains across these measures suggests that the genetically determined mechanisms are largely different between these measures of morphine sensitivity.