The Intracerebroventricular Administration of W-7, A Calmodulin Inhibitor, Attenuate the Development of Morphine Tolerance in Rats
Gholamreza Sepehri, Vahid Sheibani, Afrooz Azarang, Ali Shamsizadeh, Mohammad Reza Afarinesh, Saeed Azizollahi and Ehsan Sepehri
DOI : 10.3844/ajptsp.2010.119.124
American Journal of Pharmacology and Toxicology
Volume 5, Issue 2
Problem statement: The present study was performed to determine the effect of Intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the analgesic effect and development of tolerance to antinociceptive effect of acute and chronic morphine administration respectively. Approach: This study was carried out on male wistar rats, weighing 200-250 g. For acute experimental protocol, Morphine was injected intraperitonealy in a single dose (5 mg kg-1). For chronic experimental protocol, Morphine was administered daily (15 mg kg-1 for 8 days). The threshold to thermal nociceptive stimuli was measured by tail-flick test. In acute and chronic experiments, W-7 (0.25, 0.5 and 1 μmol/rat) was injected through ICV at different paradigms. Maximal Possible Effect percentage (MPE%) was considered as analgesia index. Results: Our result showed that W-7 (0.25, 0.5 and 1 μmol/rat) injections before acute morphine administration significantly reduced the analgesic effect of morphine compared with morphine treated group (all p<0.05). 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. Conclusion: In conclusion these data showed that acute administration of W-7 reduced the analgesics effect of morphine and 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.
© 2010 Gholamreza Sepehri, Vahid Sheibani, Afrooz Azarang, Ali Shamsizadeh, Mohammad Reza Afarinesh, Saeed Azizollahi and Ehsan Sepehri. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.