INHIBITION OF THE MORPHINE-WITHDRAWAL SYNDROME AND THE DEVELOPMENT OF PHYSICAL-DEPENDENCE BY LITHIUM IN MICE

Due to the claim that lithium (Li+) reduces morphine self-administration in dependent rats, the effects of acute and chronic Li+ treatments on naloxone-precipitated withdrawal syndrome and physical dependence development to morphine in mice chronically treated with morphine, were evaluated. Morphine dependency was induced by the ingestion of morphine through drinking water in increasing doses for 10 days. Physical dependence to morphine was observed by precipitating an abstinence syndrome with naloxone (2 mg/kg, i.p.). In the acute experiments, Li+ (1 and 10 mg/kg, i.p.) was administered 1 hr prior to challenge with naloxone to morphine-dependent mice whereas for chronic studies, mice received morphine concomitant with Li+ (1200 mg/l) as drinking fluid for 10 days. Results obtained indicate that acute Li+ administration significantly reduced the withdrawal signs, and we were unable to induce some degree of morphine dependency in co-administration of Li+ to mice receiving chronic morphine treatment as compared to chronic morphine administration alone. The present study revealed that even in mice with very much lower serum Li+ levels than the commonly accepted therapeutic range there was a significant reduction in the withdrawal signs. It has been shown that Li+ and morphine have diverse effects on the transmembrane signal control systems. The interaction of Li+ and morphine might be through these systems.