Inhibition of the spinal phosphoinositide 3-kinase exacerbates morphine withdrawal response.
The present study investigates the roles of the spinal phosphoinositide 3-kinase (PI3K) signaling pathway in naloxone-precipitated withdrawal in acute and chronic morphine-dependent mice. There are two principal findings: (1) intrathecal pretreatment with wortmannin or LY294002, two structurally unrelated PI3K inhibitors, produced a dose-dependent increase of naloxone-precipitated withdrawal jumping, which was accompanied by an increased expression of spinal Fos protein in acute and chronic morphine-dependent mice; and (2) the expression of spinal p110gamma, the catalytic subunit PI3K, in the membrane fraction was significantly down-regulated by naloxone-precipitated withdrawal in acute and chronic morphine-dependent mice. This study provides new evidence showing that inactivation of the PI3K signaling pathway in the spinal cord may be involved in the expression of morphine withdrawal.
Yang
Li
L
Jiangsu Institute of Anesthesiology, Jiangsu Key Laboratory of Anesthesiology, Xuzhou, PR China.
Zhu
Chang-Jiang
CJ
Cao
Jun-Li
JL
Zeng
Yin-Ming
YM
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009021:Morphine Dependence / Q000503:physiopathology*; D009025:Morpholines / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077191:Wortmannin; D004121:Dimethyl Sulfoxide