Effects of chronic administration of calcium-magnesium soft gels on morphine tolerance and dependence in mice

The aim of present study was to assess the effects of chronic administration of calcium-magnesium soft gels on the development of morphine tolerance and dependence in mice. Tolerance was assessed using the tail-pinch test and withdrawal signs of morphine were precipitated by injecting naloxone 2 h after the final morphine injection. CalMag capsules were given in final doses of 50/25, 25/12.5 and 12.5/6.25 mg/kg based on calcium/magnesium ratio. Similar doses of Ca and/or Mg were prepared, separately. CalMag at 50/25, 25/12.5 mg/kg and the mixture of calcium and magnesium (Ca + Mg) at 50/25, 25/12.5, 12.5/6.25 mg/kg and calcium at 50, 25 mg/kg significantly reduced the number of jumps. The number of standings was only reduced after the administration of CalMag at 50/25 mg/kg and Ca + Mg at 25/12.5 mg/kg. The development of morphine tolerance was prevented in all drug-treated groups, except the one which received 6.25 mg/kg Mg. The data suggested that combination of calcium and magnesium at 50/25 and 25/12.5 mg/kg prevented the development of tolerance and dependence. It seems that other ingredients of CalMag capsules do not have an important effect on preventing tolerance and withdrawal signs. Compared to the acute effects, chronic administration of CalMag allowed the effective dose to be reduced. Unlike the acute treatment, chronic administration of calcium alone was effective in reducing morphine tolerance and dependence, and magnesium had no significant effect on withdrawal signs, suggestive of some pharmacological adaptations.