TY  - JOUR
AU  - Sepehri, Gholamreza 
AU  - Sheibani, Vahid 
AU  - Azarang, Afrooz 
AU  - Shamsizadeh, Ali 
AU  - Afarinesh, Mohammad Reza 
AU  - Azizollahi, Saeed 
AU  - Sepehri, Ehsan 
PY  - 2010
TI  - The Intracerebroventricular Administration of W-7, A Calmodulin Inhibitor, Attenuate the Development of Morphine Tolerance in Rats
JF  - American Journal of Pharmacology and Toxicology
VL  - 5
IS  - 2
DO  - 10.3844/ajptsp.2010.119.124
UR  - https://thescipub.com/abstract/ajptsp.2010.119.124
AB  - 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.