Acute administration of pioglitazone attenuates morphine withdrawal syndrome in rat: a novel role of pioglitazone.

Abstract

Long-term exposure to opiates such is morphine induces dependence.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-?), on the morphine withdrawal syndrome in the rat.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-? antagonist, was administrated in order to evaluate the possible role of the PPAR-?.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-? independent mechanisms.