THE EFFECT OF LITHIUM ON MORPHINE-INDUCED ANALGESIA IN MICE

1. The effects of acute and chronic lithium (Li+) treatments on the an tinociception caused by morphine were studied in mice using the tail-f lick test. 2. Subcutaneous injection of morphine (10 mg/kg) caused sig nificant antinociception. 3. Acute Li+ administration (0.05, 0.1, 0.3, 1, 5 and 10 mg/kg, i.p.) alone had no significant antinociceptive eff ect but changed morphine analgesia; low doses of Li+ (0.1, 0.3 and 1 m g/kg) were found to decrease the antinociception induced by morphine w hereas higher doses of the drug (10 mg/kg) potentiated this effect. 4. The 6 day administration of Li+ with a serum level of 0.528 mM decrea sed the antinociceptive effect of morphine. 5. The effect of Li+ on mo rphine-induced analgesia persisted for 96 hr in spite of the fact that Li+ drinking was discontinued (the serum Li+ level decreased from 0.5 28 to 0.022 mM). 6. It has been reported that Li+ might change both th e binding of opioids to their receptors and biosynthesis or release of endogenous opioids. There is also a considerable body of evidence whi ch indicates that both Li+ and morphine affect phosphoinositide turnov er, intracellular calcium content and cyclic AMP level. The interactio n of two drugs may conceivably take place through these systems. 7. Th ese data suggest that the biological effects of Li+ may exist at very much lower serum Li+ levels than the commonly accepted therapeutic ran ge.