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American Journal of Pharmacology and Toxicology
Year: 2010  |  Volume: 5  |  Issue: 2  |  Page No.: 112 - 118

The Effects of W7, a Specific Calmodulin Inhibitor, to the Antinociceptive Effects of Morphine in Adrenalectomized Rats

Gholamreza Sepehri, Kayvan Yaghoobi, Vahid Sheibani, Ali Shamsizadeh and Mohammad Khaksari    

Abstract: 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.

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