Roles of Akt pathway and cell apoptosis in leptin-mediated chronic mor-phine antinociceptive tolerance / 中国病理生理杂志

ABSTRACT

AIM:To explore the roles of Akt ( also called protein kinase B ) and active caspase-3 in the leptin-mediated chronic morphine antinociceptive tolerance in rats .METHODS: A model of chronic morphine antinociceptive tolerance was established in the SD rats .The protein levels of spinal Akt and cleaved caspase-3 were tested by Western blotting.The technique of immunohistochemical staining was used to detect the immunoreactivity positive cells of phospho -rylated ( p)-Akt and cleaved caspase-3 in the spinal cord .Double staining of immunohistochemistry was used to examine the cellular location of the p-Akt and cleaved caspase-3 positive cells.RESULTS: The chronic intrathecal injection of morphine (15 μg) for 7 d markedly upregulated the spinal protein levels of p-Akt and cleaved caspase-3 in the rats.Thirty min before injection of morphine , intrathecal injection of leptin antagonist (3μg) for 7 d significantly attenuated the upreg-ulation of the protein levels of p-Akt and cleaved caspase-3 induced by chronic morphine treatment .The p-Akt was exclu-sively observed in the spinal neurons .The cleaved caspase-3 was only localized with the spinal astrocytes .Intrathecal injec-ting the inhibitors of leptin , Akt and caspase-3 ameliorated the chronic antinociceptive tolerance .CONCLUSION: The spinal Akt pathway and active caspase-3 are involved in the leptin-mediated chronic morphine antinociceptive tolerance in rats.