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

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.

Effect of sub-effective dose of GABA agonists on attenuation of morphine tolerance in rats: Behavioral and electrophysiological studies

“…: 10 mg/kg for 8 days) caused tolerance to the antinociceptive effects of morphine during the formalin test. It has been reported that intraperitoneal injection of chronic administration of morphine induces morphine tolerance in tail flick and hot plate test (Javan et al, 2003;Sepehri et al, 2010). The present data also indicated that acute administration of morphine (i.p.…”