Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats

(2014) Pioglitazone prevents morphine antinociception tolerance and withdrawal symptoms in rats. Naunyn-Schmiedeberg's Archives of Pharmacology.

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Long-term exposure to opiates induces tolerance to the analgesic effect and dependence. The purpose of the present study is to investigate the effects of pioglitazone, a peroxisome proliferator-activated receptors gamma (PPAR-γ) agonist, on the morphine-induced tolerance and dependence. Groups of rats received morphine in combination with a vehicle or pioglitazone (5, 10, 20, and 40 mg/kg) daily. Thirty minutes before pioglitazone (40 mg/kg), GW-9662, a selective PPAR-γ antagonist, (2 mg/kg) was administrated in order to evaluate the possible role of the PPAR-γ. Nociception was assessed by a tail flick apparatus, and the percentage of the maximal possible effect was calculated as well. For 9 days, rats received additive doses of morphine to induce dependence. Naloxone was administrated 2 h after the morphine last dose, and withdrawal symptoms were recorded for 45 min. Morphine administration to rats over a duration of 17 days resulted in the development of tolerance, whereas pioglitazone (40 mg/kg) delayed the day of the established tolerance for 15 days. Administration of pioglitazone also prevented morphine-induced 50 effective dose (ED50) shift to the right in the dose-response curve and increased the global analgesic effect of morphine. In addition, pioglitazone decreased the total withdrawal score significantly, whereas GW-9662 significantly reversed the pioglitazone effects on the morphine tolerance and dependence. The prevention of the morphine-induced glia activation and the proinflammatory responses were the possible mechanisms for pioglitazone effect on delaying the morphine tolerance and attenuating the dependence. © 2014 Springer-Verlag.

Item Type: Article
Keywords: 2 chloro 5 nitrobenzanilide; morphine; naloxone; pioglitazone; 2,4 thiazolidinedione derivative; 2-chloro-5-nitrobenzanilide; anilide; morphine; naloxone; narcotic analgesic agent; narcotic antagonist; peroxisome proliferator activated receptor gamma; pioglitazone, analgesic activity; animal experiment; animal model; antinociception; article; cell activation; comparative study; controlled study; drug effect; grooming; investigative procedures; jumping; licking; locomotion; long term exposure; male; morphine addiction; morphine tolerance; nonhuman; rat; rearing; shift to the right; swallowing; tail flick test; tremor; wet dog shakes; withdrawal syndrome; agonists; animal; animal behavior; antagonists and inhibitors; drug effects; drug tolerance; motor activity; pain; Substance Withdrawal Syndrome; Wistar rat, Analgesics, Opioid; Anilides; Animals; Behavior, Animal; Drug Tolerance; Male; Morphine; Motor Activity; Naloxone; Narcotic Antagonists; Pain; PPAR gamma; Rats, Wistar; Substance Withdrawal Syndrome; Thiazolidinediones
Page Range: pp. 811-821
Journal or Publication Title: Naunyn-Schmiedeberg's Archives of Pharmacology
Volume: 387
Number: 9
Publisher: Springer Verlag
Identification Number: 10.1007/s00210-014-0996-y
ISSN: 00281298
Depositing User: مهندس جمال محمودپور

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