Physical dependence induced by the voluntary consumption of morphine in inbred mice

When given a two-bottle choice between gradually increasing morphine concentrations (in 0.2% saccharin) and plain tap water, C57BL/6J mice consumed almost 90% of their daily fluid intake from the morphine-saccharin bottle, while the DBA/2J strain, in contrast, consumed 13% or less from the morphine-saccharin solution. The C57BL/6J strain consistently consumed mean daily doses of morphine sulfate in excess of 200 mg/kg, which was sufficient to induce an easily discernable withdrawal syndrome upon removal of the morphine solution, either with or without naloxone challenge. Hypothermia, tremor, wet dog shakes, jumping, and diarrhea were prominent withdrawal signs. In separate experiments, the saccharin was removed from the morphine-containing bottle, yet the C57BL/6J mice continued to prefer the morphine solution over tap water. In complete contrast to the above, mice of the DBA/2J strain rejected the morphine-saccharin solution at the lowest concentration employed, and at no time did their mean daily morphine dose exceed 20 mg/kg. Thus, morphine-saccharin preference is strongly genetically determined, and a high degree of physical dependence can result in the morphine-preferring strain. Palatability differences appear not to be the predominant explanation for these differences in morphine-saccharin consumption.