title: Acute administration of pioglitazone attenuates morphine withdrawal syndrome in rat: a novel role of pioglitazone.
abstract: BACKGROUND
  Long-term exposure to opiates such is morphine induces dependence.
  
  
  OBJECTIVE
  The purpose of the present study was to investigate the effects of the acute administration of pioglitazone, a selective agonist of peroxisome proliferator activated receptors gamma (PPAR-γ), on the morphine withdrawal syndrome in the rat.
  
  
  METHODS
  Male Wistar rats (200-250 g) were selected randomly and divided into 8 groups including 2 non-dependent groups and 6 morphine-dependent groups which were received additive doses of morphine subcutaneously at an interval of 12 h for 9 continuous days. On the ninth day, only the morning dose of morphine was injected and 2 h later, morphine withdrawal was precipitated by naloxone and then ten distinct withdrawal behaviors were recorded for 45 min. Pioglitazone (5, 10, 20 and 40 mg/kg) was gavaged 2 h before naloxone injection. It is worth noting that 1 h before the pioglitazone (40 mg/kg) gavage, GW-9662 (2 mg/kg), a selective PPAR-γ antagonist, was administrated in order to evaluate the possible role of the PPAR-γ.
  
  
  CONCLUSIONS
  The results of this study showed that administration of pioglitazone (40 mg/kg) decreased all withdrawal signs and the statistical analysis indicated that pioglitazone could attenuate the total withdrawal scores significantly. Administration of GW-9662 had no significant effect on pioglitazone attenuation effect on morphine withdrawal symptoms.Taking together, it was concluded that acute oral administration of pioglitazone prevented naloxone-precipitated withdrawal symptoms and GW-9662 could not revert its effect on morphine withdrawal syndrome. It seems that pioglitazone suppresses morphine withdrawal syndrome through PPAR-γ independent mechanisms.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: H
authors: H
authors: Ghavimi
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: A
authors: A
authors: Azarfardian
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: N
authors: N
authors: Maleki-Dizaji
authors: Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
authors: K
authors: K
authors: Hassanzadeh
authors: Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: S
authors: S
authors: Ghanbarzadeh
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: M
authors: M
authors: Charkhpour
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000813:Anilides / Q000008:administration & dosage; D000818:Animals; D008297:Male; D009020:Morphine; D009021:Morphine Dependence / Q000188:drug therapy*; D009270:Naloxone / Q000008:administration & dosage; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000701:Analgesics, Opioid; D000813:Anilides; D047495:PPAR gamma; D045162:Thiazolidinediones; D009270:Naloxone; D009020:Morphine; D000077205:Pioglitazone