A Simple Method for Evaluating Physical Dependence Liability in Rats

The single dose suppression test was applied to estimating addiction liability of compounds in rats. Morphine at a dose of 50 mg/kg was chronically administered twice daily for more than 12 weeks, and the body wt. loss following morphine withdrawal was measured for 24 hr as a parameter of abstinence syndrome. A test compound was administered to the morphine withdrawn rats and physical dependence liability was determined from the increase in body wt. The results of narcotic analgesics in this method coincided well with those seen in monkeys, however, rats appeared to be particularly sensitive to morphine-like narcotics. Narcotic antagonists, nalorphine and pentazocine, produced a severe abstinence syndrome, and antipyretics, tranquilizers, hypnotics and antihistaminics had no influence on body wt. loss in the morphine addicted rats. Thus, the single dose suppression test in rats can be useful in detecting physical dependence liability of new compounds, especially morphine-like analgesics.