Attenuating effect of β-pinene, a bicyclic monoterpene, on the acquisition and expression of morphine dependence in mice

Background and Aim : Opioid dependence is still a main concern in patients who receive opioid drugs for the alleviation of pain; however, there is no effective therapeutic approach to attenuate opioid dependence. Beta-pinene is a natural bicyclic monoterpene which possesses analgesic, anti-inflammatory and antioxidant effects. Moreover, there is evidence showing that β-pinene exhibits partial agonistic effect in μ-opioid receptors. Considering the beneficial effects of μ-opioid receptors partial agonists in preventing opioid dependence, the present study was conducted to clarify whether β-pinene is able to attenuate acquisition and expression of physical dependence to morphine.Methods : Forty eight male NMRI mice weighing 25–30 g were used in this study. In order to induce dependence, morphine sulfate was injected intraperitoneally (i.p.) once daily for 9 days. The administration of morphine was commenced with the dosage of 10 mg/kg, being increased every three days to 20 and 40 mg/kg. Control animals received normal saline + tween 80 as the vehicle. In order to evaluate the effect of β-pinene on the expression of morphine dependence, single doses of β-pinene (50, 100, and 200 mg/kg, i.p.) were administered 2 hours after the last injection of morphine on the 9th day. To assess β-pinene effect on the acquisition of dependence, multiple doses of β-pinene (25, 50 and 100 mg/kg, i.p.) were administered before each injection of morphine during the 9 days. To elicit withdrawal syndrome, naloxone (2 mg/kg, i.p.) was injected 30 min after the administration of β-pinene on the 9th day.Results : The administration of -pinene with a single dose of 200 mg/kg significantly decreased the symptoms of withdrawal syndrome including jumping, rearing, and diarrhea in morphine-dependent mice; however, the lower doses of -pinene (50 and 100 mg/kg) could not attenuate the symptoms of withdrawal syndrome. In addition, the administration of -pinene with the dosage of 100 mg/kg, i.p., once daily for 9 days, resulted in a significant reduction in jumping, rearing, and diarrhea in morphine-dependent mice. Although the lower dosage of -pinene (50 mg/kg, i.p., once daily for 9 days) could significantly decreased diarrhea and the number of jumps, no significant decrease in the number of rearing was observed. The administration of minimum dosage of -pinene (25 mg/kg, i.p., once daily for 9 days) resulted in a significant reduction in the number of jumps (bot not rearing and diarrhea) in the morphine-dependence mice.Conclusion : It was ultimately determined that β-pinene is capable of attenuating both the acquisition and expression of physical dependence to morphine in mice.

Keywords:

Beta-pinene , Morphine Dependence , Withdrawal syndrome , Monoterpene