title: Influence of idazoxan on analgesia, tolerance, and physical dependence of morphine in mice and rats in vivo.
abstract: OBJECTIVE
  To study the influence of idazoxan (Ida), an antagonist of imidazoline receptors (I-R), on analgesia, tolerance, and physical dependence of morphine.
  
  
  METHODS
  The effects of Ida on pain threshold and morphine analgesia were observed in mouse acetic acid writhing test and 55 degrees C hot plate test. The effect of Ida on morphine tolerance and physical dependence were observed in mouse tolerant model and in mice and rat models.
  
  
  RESULTS
  Ida (3-9 mg/kg) significantly decreased the pain threshold by 120% in acetic acid writhing test and by 39% in 55 degrees C hot plate test of mice, respectively. It inhibited the analgesic effect of morphine in a dose-dependent manner. Ida promoted the development of tolerance to morphine in mice and induced the abstinence syndrome in morphine-dependent mice and rats similar to naloxone.
  
  
  CONCLUSIONS
  I-R and its endogenous ligand agmatine might participate in the pain threshold and influence morphine analgesia as well as negatively regulate tolerance to and physical dependence on morphine.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. QinBY@nic.bmi.ac.cn
authors.forename: R B
authors.initials: RB
authors.lastname: Su
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Gao
authors.forename: G
authors.initials: G
authors.lastname: Pei
authors.forename: B Y
authors.initials: BY
authors.lastname: Qin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D019329:Idazoxan / Q000494:pharmacology*; D007093:Imidazoles; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009021:Morphine Dependence / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000037:antagonists & inhibitors
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D009020:Morphine; D019329:Idazoxan