Changes in morphine self-administration in rats induced by prostaglandin E1 and naloxone.

Interactions of prostaglandin E1 (PGE1) with morphine have been reported in several test systems and an hypothesis has been advanced for a role of prostaglandins in morphine analgesia and physical dependence. In rats self-administering morphine intravenously, a simultaneous and continuous infusion of naloxone hydrochloride at 56 to 560 mug/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE1 by itself at 56 or 180 mug/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE1 at 180 mug/kg/day did not potentiate the increase caused by naloxone (56 or 180 mug/kg/day) when it was added to the naloxone infusion. These results do not support a role for prostaglandins in the behavioral aspects of morphine addiction. However, larger doses of PGE1 (1 and 1.8 mg/kg/day), which were without overt effects in normal rats, caused severe and incapacitating prostration in morphinized rats.