Drug Res (Stuttg) 2015; 65(3): 113-118
DOI: 10.1055/s-0033-1364035
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Acute Administration of Pioglitazone Attenuates Morphine Withdrawal Syndrome in Rat: A Novel Role of Pioglitazone

H. Ghavimi
1  Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2  Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
A. Azarfardian
1  Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
N. Maleki-Dizaji
1  Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
K. Hassanzadeh
3  Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
4  Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
,
S. Ghanbarzadeh
2  Student Research Committee and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
M. Charkhpour
1  Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 20. Dezember 2013

accepted 08. Januar 2014

Publikationsdatum:
06. Februar 2014 (online)

Abstract

Background:

Long-term exposure to opiates such is morphine induces dependence.

Purpose:

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.

Result and Discussion:

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.

Conclusion:

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.