Mouse model demonstrates strain differences in susceptibility to opioid side effects

Individual differences have been observed in responses to opioid drugs, including common side effects. In this study, the inbred mouse strains A/J and C57BL/6J were used to determine whether their specific strain differences correlate with differences in susceptibility to respiratory depression and constipation. To measure the effects of morphine on respiration, morphine at 15 and 40 mg/kg was injected subcutaneously. Respiratory parameters were then measured 30 and 60 min later. To measure the effects on constipation, 5, 15, 40, and 60 mg/kg doses were administered subcutaneously three times daily for three days. Gastrointestinal transit distance was then measured using the charcoal bolus test. C57BL/6J mice showed a greater degree of change in several respiratory parameters, resulting in more pronounced respiratory depression. C57BL6J mice also showed significantly more constipation than A/J mice with 40 and 60 mg/kg morphine doses. This study demonstrates that the strain differences between A/J and C57BL/6J mice have a major effect on opioid-induced constipation and respiratory depression. These correlations are of great clinical interest, as they could lead to the development of methods for reducing side effects.