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*


研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)1027-1030
期刊Acta Pharmacologica Sinica
出版狀態Published - 8月 2004


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