title: The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence.
abstract: BACKGROUND
  Previous 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.
  
  
  METHODS
  We used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5mg/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 75mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5mg/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 5mg/kg) before morphine administrations.
  
  
  RESULTS
  Morphine (40mg/kg, subcutaneous; sc), but not O-1602 (5mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1mg/kg, but not 5mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 at the doses of 0.2, 1 and 5mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5mg/kg by decreasing jumps and diarrhea during withdrawal syndrome.
  
  
  CONCLUSIONS
  The present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.
authors.affiliation: Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohaddeseh Sadat
authors.initials: MS
authors.lastname: Alavi
authors.affiliation: Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinzadeh
authors.affiliation: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shamsizadeh
authors.affiliation: Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: roohbakhsha@mums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Roohbakhsh
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000031:analogs & derivatives; D003213:Conditioning, Psychological / Q000187:drug effects*; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy*; D012118:Resorcinols / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D003510:Cyclohexanes; D012118:Resorcinols; D002185:Cannabidiol; C568537:O-1602 compound; D009020:Morphine
keywords: GPR55 protein; Morphine; O-1602; Opiate dependence; Reward