The 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 micromol/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 micromol/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.
Sepehri
Gholamreza
G
Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. gsepehri@yahoo.com
Sheibani
Vahid
V
Azarang
Afrooz
A
Shamsizadeh
Ali
A
Afarinesh
Mohammad Reza
MR
Azizollahi
Saeed
S
Sepehri
Ehsan
E
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D000701:Analgesics, Opioid; D002147:Calmodulin; D004791:Enzyme Inhibitors; D013449:Sulfonamides; C017967:W 7; D009020:Morphine