• Acta Pharmacol. Sin. · Aug 2004

    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, and Cheng-Yuang Lu.
    • Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Taiwan, China.
    • Acta Pharmacol. Sin. 2004 Aug 1; 25 (8): 1027-30.

    AimTo investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats.MethodsTail-flick test as pain threshold measurement and intrathecal injection techniques were used.ResultsIntrathecal 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).ConclusionCdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

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