title: Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathway.
abstract: Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1-40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5-20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). L-NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of L-NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and L-NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway.
authors: Department of Pharmacology, School of Medicine and Interdisciplinary Neuroscience Research Program, Medical Sciences/University of Tehran, Tehran, Iran.
authors: Noushin
authors: N
authors: Yahyavi-Firouz-Abadi
authors: Pouya
authors: P
authors: Tahsili-Fahadan
authors: Mohammad Hossein
authors: MH
authors: Ghahremani
authors: Ahmad Reza
authors: AR
authors: Dehpour
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012201:Reward
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009020:Morphine; D019001:Nitric Oxide Synthase; D008550:Melatonin; D019331:NG-Nitroarginine Methyl Ester