Assessment of physical dependence-inducing capacity of narcotic agonists and antagonists in rats by intermittent infusion technique.

Narcotics and other drugs were injected into the rat once an hour for about 1 week. Morphine and codeine showed physical dependency with a maintenance dose as low as 9.6 mg/kg/day. Development of dependence was also recorded in rats treated with cyclazocine (9.6 mg/kg/day) and pentazocine (96 mg/kg/day), and suspected in the levallorphan-treated (9.6 mg/kg/day) rats. Dependence on pethidine, which is known to be difficult to detect by the usual method in rats, also developed in this experiment (96 mg/kg/day), but it was estimated to be of lesser degree than that of codeine. Dependence on allazocine (9.6 mg/kg/day) and aminopyrine (96 mg/kg/day) did not develop. Barbital dependence (96 mg/dg/day) was induced, but it was distinguished from morphine-like drugs by the naloxone precipitation test and by substitution experiments. Cross-dependence between morphine and dependence-inducing drugs was investigated. Withdrawal weight loss in the morphine-dependent rats was suppressed or attenuated by pentazocine, pethidine, and codeine. Withdrawal weight loss in the rats dependent on cyclazocine, pentazocine, pethidine, or codeine was suppressed by morphine. Intermittent infusion of pentazocine at longer intervals induced dependence not as severe as that induced by 1-h infusion.