intracerebroventricular [ICV] administration of w-7, a calmodulin inhibitor, attenuates the development of morphine tolerance in rats

The present study was performed to determine the effect of intracerebroventricular [ICV] administration of W- 7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. This study was carried out on male wistar rats, weighing 200-250 g. Morphine was administered daily [15 mg/kg for 8 days]. The threshold to thermal nociceptive stimuli was measured by tail-flick test. W-7 [0.25, 0.5 and 1 micro mol/rat] was injected through ICV. Maximal possible effect percentage [MPE%] was considered as analgesia index. Our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of W-7 [0.5 and 1 micro mol/rat] decreased the development of tolerance to it. In conclusion these data showed that 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

[Differences of intensities regarding withdrawal signs in experimental methods for inducing morphine dependency]

In the present study, we compared the intensity of physical dependency, mortality rate and weight changes in some common methods for inducing morphine dependency. Six common different methods for morphine dependency were chosen in wistar rats. In all methods, morphine dependency was induced by repeated morphine injection. Precipitation of morphine withdrawal signs were performed on the last day in each method, 4 hours after the last morphine injection for 20 minutes. The withdrawal signs included: vertical jumping, wet dog shakes, diarrhea, teeth chattering, ptosis, head shakes and rearing. Our results demonstrated that all groups of treated rats showed withdrawal signs following naloxone challenge. However, the intensities of withdrawal signs [vertical jumping, wet dog shakes, diarrhea, teeth chattering, head shakes and rearing] were significantly different among these methods. Also, mortality rate and amount of weight loss were significantly different among the different methods. This study demonstrates that different experimental methods of morphine dependency can induce different intensities of withdrawal signs, mortality rate and weight loss

W-7 [a calmodulin antagonist] inhibits carrageenan-induced paw edema in intact and adrenalectomized rats

The aim of present study was to investigate the effect of W-7, a calmodulin antagonist, on a carrageenan-induced rat's paw edema. W-7[50 micro Mol/kg] was given intraperitoneally synchronous with the intraplantar injection of 0.1 ml of 0.5% carrageenan solution. After for hours, paw edema was assessed by calculating the paw volume changes which measured by hydroplethysmometer. In adrenalectomized rats, both adrenal glands were removed. Treatment of animals with W-7 reduced carrageenan-induced paw edema by 50%. In adrenalectomized rats, W-7 was also effective in reduction of paw edema [52%]. There was no significant difference between the effect of W-7 in adrenalectomized and control animals. Our findings suggest that W-7 as calmodulin inhibitor reduce carrageenan-induced paw edema and the inhibitory effect W-7 on edema formation appears not to be dependent on adrenal function