Research Article Open Access

The Intracerebroventricular Administration of W-7, A Calmodulin Inhibitor, Attenuate the Development of Morphine Tolerance in Rats

Gholamreza Sepehri1, Vahid Sheibani2, Afrooz Azarang2, Ali Shamsizadeh2, Mohammad Reza Afarinesh1, Saeed Azizollahi2 and Ehsan Sepehri1
  • 1 , Afganistan
  • 2 ,
American Journal of Pharmacology and Toxicology
Volume 5 No. 2, 2010, 119-124

DOI: https://doi.org/10.3844/ajptsp.2010.119.124

Submitted On: 2 January 2010 Published On: 30 June 2010

How to Cite: Sepehri, G., Sheibani, V., Azarang, A., Shamsizadeh, A., Afarinesh, M. R., Azizollahi, S. & Sepehri, E. (2010). The Intracerebroventricular Administration of W-7, A Calmodulin Inhibitor, Attenuate the Development of Morphine Tolerance in Rats. American Journal of Pharmacology and Toxicology, 5(2), 119-124. https://doi.org/10.3844/ajptsp.2010.119.124

Abstract

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.

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Keywords

  • Calmodulin inhibitor (W-7)
  • morphine
  • tolerance
  • tail-flick test
  • pain
  • rat