The crucial roles of nociceptin opioid peptide (NOP) receptor in attenuating relapse in morphine/methamphetamine (poly-drug) dependence model

BACKGROUND: Effective treatment for relapse prevention to poly-drug is still not yet available although this public health issue is alarming. Our previous study has proved that a combination of buprenorphine/naltrexone treatment successfully attenuated relapse (reinstatement) in morphine/methamphetamine (poly-drug) dependent mice using a conditioned place preference (CPP) model. The net pharmacological effects of buprenorphine/naltrexone treatment combination are agonism at the kappa opioid receptor and a partial agonist at the NOP receptor. Thus, this recent study aimed to investigate if the NOP receptor is the key opioid receptor that is responsible in attenuating relapse to this poly-drug addiction. METHOD: The previous CPP protocol was maintained. The male Swill albino mice were injected with 6.0 mg/kg SB 612111 (a selective NOP antagonist) 30 minutes prior to the administration of the same dose of buprenorphine/naltrexone combination (0.3 mg/kg morphine and 1.0 mg/kg, respectively). The priming doses of poly-drug (2.5 mg/kg morphine/1.0 mg/kg methamphetamine) were given 10 minutes after. The percentage of time spent at the drug-paired compartment was compared between groups. RESULTS: The results revealed that the priming doses of poly-drug induced relapse in the group of mice that received SB 612111 prior to buprenorphine/naltrexone treatment (53.81 ± 11.23 %, n = 6) which was significantly different compared to its baseline (-5.37 ± 6.41 %, n = 9, p < 0.05). In contrast, relapse was significantly attenuated in the group of mice that only received buprenorphine/naltrexone treatment prior to drug priming (19.14 ± 16.89 %, n = 5) which was not significantly different from its baseline (-16.14 ± 4.81 %, n = 13). CONCLUSION: From these results, it is suggested that an agonist activity at the NOP receptor is crucial in preventing relapse to morphine/methamphetamine (poly-drug) dependence. Hence, further investigation needs to be done to evaluate the involvement of this receptor at the brain level.