Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

Acta Pharmacol Sin. 2004 Aug;25(8):1027-30.

Abstract

Aim: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats.

Methods: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used.

Results: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 microg/h for 5 d. Co-administration of intrathecal roscovitine 1 microg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose-response curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response).

Conclusion: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Drug Tolerance*
  • Injections, Spinal
  • Male
  • Morphine / pharmacology*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Purines / administration & dosage
  • Purines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Roscovitine

Substances

  • Analgesics, Opioid
  • Purines
  • Roscovitine
  • Morphine
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, rat
  • Cyclin-Dependent Kinases