كالمودولين اثرات ضددردي مورفين را در موش هاي صحرايي تقويت مي كند

Calmodulin Potentiates the Antinociceptive Effects of Morphine in Rats

Background and Objectives: Calmodulin is involved in signaling pathways of opioid receptors. The present study was performed to determine the effect of chronic intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the development of morphine tolerance. Materials and Methods: This experimental study was carried out on 75 male wistar rats weighing 200-250 g. The cannula was placed in the lateral ventricle of ratʹs brain according to the Paxinos and Watson atlas using the stereotaxic instrument. Rats were allowed a 7 day recovery period after the surgery for implantation of the cannula. Morphine was injected intraperitoneally based on a daily dose of 15mg/kg for 8 days. The development of tolerance to analgesic effects of morphine was measured on days I, 3, 5 and 8 by Tail-Flick test. W-7 (0.25, 0.5 and I micromol/rat) was injected as ICV each day 10 minutes prior the morphine administration. On days that Tail-Flick test was performed W-7 was administered after the test. Results: Chronic administration of morphine alone for 8 days induced tolerance to its antinociceptive effect. ICV administration of W-7 in dose of 0.5 and 1 micomollrat could prevent the development of morphine tolerance. However administration of W-7 in dose of 0.25 micomol/rat could not prevent the development of morphine tolerance Conclusion: Chronic ICV administration of W-7 (a specific calmodulin inhibitor) inhibited the development of morphine tolerance. These results indicate that calmodulin and calmodulin- dependent pathways may playa role in the morphine tolerance process.