Central Endothelin-B Receptor Stimulation Does Not Affect Morphine Analgesia in Rats

Abstract

Several neurotransmitter mechanisms have been proposed to play a role in the actions of morphine. We reported that centrally administered endothelin A (ET_A) receptor antagonists potentiate morphine analgesia in rats. It has also been reported that ET_B agonist, IRL1620, has antinociceptive action mediated through opiate receptors in the periphery. The present study was conducted to determine if central ET_B receptors are involved in analgesic actions of morphine. The effect of intracerebroventricular (i.c.v.) administration of ET_B receptor agonist, IRL1620, on morphine-induced analgesia and hyperthermia was determined in the rat. Morphine (4 mg/kg, s.c.) produced a significant increase (84%) in tail-flick latency compared to the control group and the analgesic response lasted for 4 h. IRL1620 (30 µg, i.c.v.) did not produce any increase (16%) in tail-flick latency over the 5-hour observation period in vehicle-treated rats. Pretreatment with IRL1620 (3, 10, and 30 µg, i.c.v.) did not have any significant effect on the intensity and duration of morphine (4 mg/kg, s.c.)-induced analgesia. Morphine (4 mg/kg, s.c.) administration produced an increase in body temperature compared to the control group. In vehicle-pretreated rats, IRL1620 (30 µg, i.c.v.) did not produce any change in body temperature. The morphine-induced hyperthermic effect was not altered in IRL1620-pretreated rats. These studies demonstrate that IRL1620, a specific ET_B receptor agonist, did not affect the morphine-induced analgesic and hyperthermic effect in rats. It can be concluded that central ET_B receptors are not involved in modulation of pharmacological actions of morphine.