Examining the effect of the CaMKII inhibitor administration in the locus coeruleus on the naloxone-precipitated morphine withdrawal signs in rats

Behav Brain Res. 2012 Jan 15;226(2):440-4. doi: 10.1016/j.bbr.2011.09.043. Epub 2011 Oct 10.

Abstract

Drug addiction is an occurrence with physiological, psychological, and social outcomes. Repeated drug exposure causes neuronal adaptations and dependency. It has been shown that CaMKIIα enzyme contributes to morphine dependency. The locus coeruleus nucleus has been implied in the morphine withdrawal syndrome. This research focuses on the behavioral and molecular adaptations that occur in the locus coeruleus neurons in response to the chronic morphine exposure. Adult male Wistar rats were injected by morphine sulfate (10 mg/kg/s.c.) at an interval of 12 h for a period of nine subsequent days. On the tenth day, naloxone (1 mg/kg/i.p.) was injected 2 h after the morphine administration. Somatic withdrawal signs were investigated for 30 min. We concluded that the inhibition of CaMKIIα by administration of KN-93, the specific inhibitor of this enzyme, significantly attenuated some of the withdrawal signs. In molecular method, the expression of CaMKIIα protein has been enhanced in locus coeruleus of the morphine dependent rats. These findings indicate that CaMKIIα may be involved in the modulation of the naloxone-induced withdrawal syndrome, and treatment with KN-93 may have some effects on this system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / administration & dosage
  • Benzylamines / pharmacology
  • Benzylamines / therapeutic use*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / biosynthesis
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Humans
  • Locus Coeruleus / drug effects*
  • Locus Coeruleus / enzymology*
  • Male
  • Microinjections
  • Morphine / adverse effects*
  • Naloxone / pharmacology*
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / enzymology
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*

Substances

  • Benzylamines
  • KN 92
  • Sulfonamides
  • KN 93
  • Naloxone
  • Morphine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2