Intrathecal cdk5 inhibitor,roscovitine,attenuates morphine antinociceptive tolerance in rats
摘要
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 anantinociceptive 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 doseCresponse curve to the left when co-administered withmorphine during tolerance induction, and caused a 67 % reduction in the increase in the EDs0 of morphine （doseproducing 50 % of the maximum response）. CONCLUSION： Cdk5 modulation is involved in the antinociceptivetolerance of morphine.Intrathecal roscovitine administration could attenuate this tolerance development.