Effects of Magnesium Oxide Nanoparticles on Depression- Like Behavior Induced by Naloxone and Morphine Withdrawal

Background: Our previous studies indicated that nanoparticles of magnesium oxide (nano-MgO) can affect some of morphine withdrawal signs such as anxiety, but their interaction with opioidergic system activity in depression- like behavior induced by morphine withdrawal is not clear. Objectives: The present study aimed at investigating the effects of nano-MgO on depression induced by naloxone and morphine withdrawal in animals. Methods: Adult male NMRI mice were divided in 2 main groups. For the control group, intraperitoneal (i.p.) injection of nano- MgO (1, 2.5 and 5 mg/kg) or naloxone (3 and 5 mg/kg) and coinjections of naolxone5 before and after nano-MgO2.5 mg/kg were done. The morphine withdrawal group received saline or nano-MgO 2.5, 5 and 10 mg/kg as acute (a single injection at the test day) and chronic injection (coinjected with morphine for 4 days). To develop morphine dependency, increasing doses of 20, 40, and 80 mg/kg morphine were injected subcutaneously for 4 days. Then, mice received a final morphine injection (40mg/kg) 3 hours prior to naloxone (5 mg/kg (i.p.)) on the test day. Depression- like behavior was assessed by the tail suspension test. Results: Naloxone 3 and 5mg/kg induced depression (P 0.05 and P 0.01, respectively), while acute injection of nano- MgO2.5mg/kg after naloxone5 mg/kg improved depression (P 0.01). Morphine withdrawal has induced depression in addicted mice (P 0.05), while acute injection of nano-MgO2.5 mg/kg (P 0.05) and nano-MgO 5 and 10 mg/kg (P 0.01) reduced it. Conclusions: Nano-MgO can reduce depression- like behavior induced by naloxone and morphine withdrawal in animals probably by interaction with opioid receptors.