Chronic co-administration of nalbuphine attenuates the development of opioid dependence

Nalbuphine is an agonist of κ-opioid receptors and a partial agonist of μ-opioid receptors, which can stimulate κ-receptors and antagonize the acute rewarding effects of morphine. It is widely used either as an analgesic or as an adjuvant with morphine. This present study aimed to compare the acute and chronic effects of nalbuphine on the naloxone-precipitated opiate-withdrawal in rats. Male adult Wistar albino rats (150–175 g, n = 160) were made physically dependent by administrating increasing dose of morphine (5–25 mg/kg; i.p.). Motor activity was measured for 25 min at five-minute intervals on days 0, 1, 3, 5, and 6 using Activity Monitor (Coulbourn Instruments, Inc. USA) and True-scan software. The withdrawal was precipitated with intraperitoneal injections of naloxone (1 mg/kg) 4 h after the last injection of morphine. Somatic signs of withdrawal were scored using the global Gellert-Holtzman rating scale. Nalbuphine was co-administered acutely and chronically at various doses (0.1, 0.3, 1.0, and 3.0 mg/kg; i.p.) with morphine. In general, the opiate-dependent rats showed a significant increase in motor activity and Gellert-Holtzman score. Animals co-administered with chronic doses of nalbuphine showed a significant decrease in motor activity and naloxone-precipitated opiate withdrawal, but acute nalbuphine treatment did not attenuate the development of opioid dependence. These findings suggest that nalbuphine could be used as an effective pharmacological adjunct in the treatment of opioid addiction. •Opioids such as morphine are of enormous therapeutic importance in the control of moderate to severe pain•Unfortunately repeated treatment with morphine produces physical dependence characterized by tolerance and dependence•Nalbuphine an opioid mixed agonist-antagonist block the morphine-induced rewarding effects•Chronic co-administration of nalbuphine with morphine was found effective and significant in attenuating the opioid tolerance and dependence in rats•This could have a great potential for the development of new therapies to prevent opiate addiction, especially in the treatment of chronic pain