Premium
Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathway
Author(s) -
YahyaviFirouzAbadi Noushin,
TahsiliFahadan Pouya,
Ghahremani Mohammad Hossein,
Dehpour Ahmad Reza
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00422.x
Subject(s) - melatonin , morphine , nitric oxide , pharmacology , conditioned place preference , analgesic , nitric oxide synthase , chemistry , medicine
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.