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.
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.
Authors: Stephen J Glatt; Jessica A Su; Shao C Zhu; Ruimin Zhang; Bo Zhang; Jixiang Li; Xiaobo Yuan; Jianhua Li; Michael J Lyons; Stephen V Faraone; Ming T Tsuang Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2006-09-05 Impact factor: 3.568
Authors: Stephen J Glatt; Jessica A Lasky-Su; Shao C Zhu; Ruimin Zhang; Bo Zhang; Jixiang Li; Xiaobo Yuan; Jianhua Li; Michael J Lyons; Stephen V Faraone; Ming T Tsuang Journal: Drug Alcohol Depend Date: 2008-06-06 Impact factor: 4.492
Authors: Tej K Pareek; Jason Keller; Sashi Kesavapany; Nitin Agarwal; Rohini Kuner; Harish C Pant; Michael J Iadarola; Roscoe O Brady; Ashok B Kulkarni Journal: Proc Natl Acad Sci U S A Date: 2006-12-28 Impact factor: 11.205