THE INTRACEREBROVENTRICULAR (ICV) ADMINISTRATION OF W-7, A CALMODULIN INHIBITOR, ATTENUATES THE DEVELOPMENT OF MORPHINE TOLERANCE IN RATS

The present study was performed to determine the effect of intracerebroventricular (icv) administration of w- 7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. this study was carried out on male wistar rats, weighing 200-250 g. morphine was administered daily (15 mg/kg for 8 days). the threshold to thermal nociceptive stimuli was measured by tail-flick test. w-7 (0.25, 0.5 and 1 μmol/rat) was injected through icv. maximal possible effect percentage (mpe %) was considered as analgesia index. our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of w-7 (0.5 and 1 μmol/rat) decreased the development of tolerance to it. in conclusion these data showed that chronic injection of w-7 inhibited the development of morphine tolerance which indicates that calmodulin and its dependent pathways may play a role in the morphine tolerance processes.