Inhibition of the spinal phosphoinositide 3-kinase exacerbates morphine withdrawal response

Neurosci Lett. 2006 Aug 14;404(1-2):237-41. doi: 10.1016/j.neulet.2006.05.056. Epub 2006 Jun 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Chromones / pharmacology*
  • Dimethyl Sulfoxide / pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morphine Dependence / physiopathology*
  • Morpholines / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology*
  • Substance Withdrawal Syndrome / physiopathology*
  • Wortmannin

Substances

  • Androstadienes
  • Chromones
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Wortmannin
  • Dimethyl Sulfoxide