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

Cheng Haung Wang, Tsung Hsing Lee, Yi Jung Tsai, Jong Kang Liu, Yann Jang Chen, Lin Cheng Yang, Cheng Yuan Lu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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 μg/h for 5 d. Co-administration of intrathecal roscovitine 1 μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED 50 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.

Original languageEnglish
Pages (from-to)1027-1030
Number of pages4
JournalActa Pharmacologica Sinica
Issue number8
StatePublished - Aug 2004


  • Cyclin-dependent kinase 5
  • Morphine
  • Roscovitine


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