Central administration of prostaglandin E2 facilitates while F2 alpha attenuates acute dependence upon morphine rats

The effects of prostaglandin D2 (PGD2), E2 (PGE2), and F2 alpha (PGF2 alpha) 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 microliter/minute of a solution containing 2.3 mM CaCl2 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 had 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 PGE2, which did not alter the initial suppressant action of morphine, potentiated the naloxone effect. A dose of PGF2 alpha, which likewise did not alter the initial action of morphine, antagonized the naloxone effect. However, a higher dose of PGF2 alpha which enhanced the initial morphine effect, caused an enhanced naloxone effect as well.(ABSTRACT TRUNCATED AT 250 WORDS)