The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence

BackgroundPrevious studies show that some non-CB1/non-CB2 effects of cannabinoids are mediated through G protein coupled receptor 55 (GPR55). As this receptor is activated by some of cannabinoid receptor ligands and is involved in the modulation of pain, it was hypothesized that this receptor may also interact with opioids. This study examined the effect of atypical cannabinoid O-1602 as a GPR55 agonist on morphine-induced conditioned place preference (CPP) and physical dependence.MethodsWe used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP in male mice. The locomotor activities of mice were also recorded. Moreover, repeated administration of morphine (50, 50 and 75 mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5 mg/kg, ip). The effect of O-1602 on the development of morphine physical dependence was assessed by injection of O-1602 (0.2, 1 and 5 mg/kg) before morphine administrations.ResultsMorphine (40 mg/kg, subcutaneous; sc), but not O-1602 (5 mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1 mg/kg, but not 5 mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5 mg/kg. O-1602 at the doses of 0.2, 1 and 5 mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5 mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5 mg/kg by decreasing jumps and diarrhea during withdrawal syndrome.ConclusionsThe present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.