Protective effects of calcium-magnesium soft gels in morphine tolerant and dependent mice.

The present study was aimed at evaluating the acute effects of Calcium-Magnesium soft gels (CalMag) in morphine tolerant and dependent mice. Mice were rendered tolerant and dependent on morphine by subcutaneous injection of morphine over a fixed time period. Withdrawal signs were precipitated by injecting naloxone 2 h after the final injection of morphine. The tail-pinch assay was used to investigate the effects of various compounds on the development and reversal of morphine tolerance. Acute injection of CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium) significantly reduced the number of jumps, stands and fast breathing in morphine dependent mice. Co-administration of calcium (50 mg/kg) and magnesium (25 mg/kg) was also effective in preventing the development of morphine tolerance and dependence. Administration of calcium (up to 50 mg/kg) alone did not significantly block the development of tolerance and dependence. The mean latency to pain was significantly increased in animals pretreated with CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium). The mixture of calcium and magnesium at specific concentrations seem to be critical for preventing the development of morphine tolerance and dependence.