Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats.

Rats were made dependent on morphine by mixing the drug with their only source of food. Naltrexone (0.5 mg/kg) injection precipitated a syndrome of withdrawal signs including weight loss. Pretreatment with the selective kappa agonist, U-50,488H (1.0, 30.0 or 10.0 mg/kg), generally had no effects on the signs of morphine withdrawal. In other subjects, U-50,488H was repeatedly administered (1.0, 3.0 or 10.0 mg/kg per 12 h) during the development of morphine dependence. In these subjects, the course of naltrexone-precipitated withdrawal was unchanged. These results suggest that agonist activity at kappa receptors is not sufficient to alter morphine dependence or withdrawal.