Central administration of prostaglandin E 2 facilitates while F 2α attenuates acute dependence upon morphine rats

Abstract

The effects of prostaglandin D 2 (PGD 2), E 2 (PGE 2), and F 2α (PGF 2α) on acute dependence on morphine were investigated. Five mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and implanted with permanent guide cannulas with the tips of the cannulas in their right lateral brain ventricles. The experimental protocol began with a 45 minute behavioral session and brain infusion (1 μl/minute of a solution containing 2.3 mM CaCl 2 in 0.9% saline, ICV). Fifteen minutes into the session the rats were injected with 7.5 mg morphine/kg (IP). Beginning 2.25 hours later the brain infusion was reinitiated during a second 45 minute behavioral session which was interrupted after 15 minutes to inject 1.0 mg naloxone/kg (IP). In several experiments a dose of PG, which did not in-and-of-itself affect behavior, was added to the infusion medium. Prior to the naloxone injection it was ascertained that the behavioral effects of morphine has dissipated. The injection of naloxone or saline did not alter behavior of the rats while they were being infused with a PG or PG vehicle. Injection of naloxone, 3 hours after the injection of morphine, resulted in a significant suppression of FR 30 behavior (withdrawal). A dose of PGE 2, which did not alter the initial suppressant action of morphine, potentiated the naloxone effect. A dose of PGF 2α, which likewise did not alter the initial action of morphine, antagonized the naloxone effect. However, a higher dose of PGF 2α which enhanced the initial morphine effect, caused an enhanced naloxone effect as well. PGD 2 did not alter the actions of morphine or naloxone. It is concluded that infusion of various PGs into the brains of rats differentially alters their responsiveness to morphine and dependence upon the opiate. It is further concluded that the dose and initial interactive effect of PGs and morphine are important determinants of the direction and degree of the expression of withdrawal.