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  • Title: The intracerebroventricular (ICV) administration of W-7, a calmodulin inhibitor, attenuates the development of morphine tolerance in rats.
    Author: Sepehri G, Sheibani V, Azarang A, Shamsizadeh A, Afarinesh MR, Azizollahi S, Sepehri E.
    Journal: Pak J Pharm Sci; 2010 Apr; 23(2):170-4. PubMed ID: 20363694.
    Abstract:
    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 micromol/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 micromol/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.
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