TY  - JOUR
AU  - Sepehri, Gholamreza 
AU  - Yaghoobi, Kayvan 
AU  - Sheibani, Vahid 
AU  - Shamsizadeh, Ali 
AU  - Khaksari, Mohammad 
PY  - 2010
TI  - The Effects of W7, a Specific Calmodulin Inhibitor, to the Antinociceptive Effects of Morphine in Adrenalectomized Rats
JF  - American Journal of Pharmacology and Toxicology
VL  - 5
IS  - 2
DO  - 10.3844/ajptsp.2010.112.118
UR  - https://thescipub.com/abstract/ajptsp.2010.112.118
AB  - Problem statement: This study was performed to evaluate the effect of W7 (specific
calmodulin inhibitor) on morphine induced analgesia in Adrenalectomized (ADX) rats by tail-flick
test. Approach: Tolerance to morphine was induced in male Wistar rats by daily injections of
morphine (15 mg kg-1, i.p) for 8 days. Adrenalectomy was performed under general anesthesia with
intraperitoneal (i.p) injection of ketamine (50 mg kg-1) and xylazine (5 mg kg-1). In sham operated
animals only the incision was made but adrenals were not removed. Five days after surgery, W7 (0.25,
0.5, 1 and 2 μmol rat-1) was injected Intracerebroventricularlly (ICV) concomitant with morphine (15 mg
kg-1, i.p) for 8 consecutive days. Tail Flick Latency (TFL) was used to assess the nociceptive response at
days 1, 3, 5 and 8 before and 30 min after morphine administration in sham operated and ADX rats.
Maximal Possible Effect percentage (MPE %) was considered as analgesia index. Results: The results
showed that daily morphine injection caused a marked analgesia in rats, but MPE % decreased
significantly after 8 days which shows the development of tolerance to morphine (p<0.05). MPE %
following morphine treatment in ADX rats was significantly greater than sham operated rats (p<0.05)
and W7 (0.5, 1 and 2 micromol/rat/ICV) significantly attenuated the development of tolerance to
morphine in ADX rats compared to sham operated rats (p<0.05 and p<0.001). Corticosterone
replacement reversed the effect of W7 on ADX rats (p<0.005). Conclusion: The results of this study
showed that hypothalamic- pituitary-adrenal axis and calmodulin may play a role in the development
of tolerance to morphine antinociceptive effects in rats.