CALMODULIN POTENTIATES THE ANTINOCICEPTIVE EFFECTS OF MORPHINE IN RATS

Calmodulin Potentiates the Antinociceptive Effects of Morphine in Rats A. Azarang [1] , A. Shamsizadeh [2] , V. Sheibani [3] , S. Azizollahi1, Gh.R. Sepehri [4] , M. Allahtavakoli [5] , M.E. Rezvani 5 , M. Mahmoodi [6] Received: 28/06/08 Sent for Revision: 04/02/09 Received Revised Manuscript: 14/02/09 Accepted: 16/03/09 Background and Objectives: Calmodulin is involved in signaling pathways of opioid receptors. The present study was performed to determine the effect of chronic intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the development of morphine tolerance. Materials and Methods: This experimental study was carried out on 75 male wistar rats weighing 200-250 g. The cannula was placed in the lateral ventricle of rat's brain according to the Paxinos and Watson atlas using the stereotaxic instrument. Rats were allowed a 7 day recovery period after the surgery for implantation of the cannula. Morphine was injected intraperitoneally based on a daily dose of 15mg/kg for 8 days. The development of tolerance to analgesic effects of morphine was measured on days 1, 3, 5 and 8 by Tail-Flick test. W-7 (0.25, 0.5 and 1micromol/rat) was injected as ICV each day 10 minutes prior the morphine administration. On days that Tail-Flick test was performed W-7 was administered after the test. Results: Chronic administration of morphine alone for 8 days induced tolerance to its antinociceptive effect. ICV administration of W-7 in dose of 0.5 and 1 micomol/rat could prevent the development of morphine tolerance. However administration of W-7 in dose of 0.25 micomol/rat could not prevent the development of morphine tolerance Conclusion: Chronic ICV administration of W-7 (a specific calmodulin inhibitor) inhibited the development of morphine tolerance. These results indicate that calmodulin and calmodulin- dependent pathways may play a role in the morphine tolerance process. Key words: Calmodulin, Tolerance, Morphine, W-7 Funding: This study was supported by Kerman neuroscience research center. Conflict of interest: None declared. Ethical approval: The Ethics Committee of Kerman Neuroscience Research Center, approved the study. [1] - General Physicion, Neuroscience Research Center, University of Medical Sciences, Kerman, Iran [2] - Assistant Prof., Dept. of Physiology and Pharmacology, Medical School, University of Medical Sciences, Rafsanjan, Iran (Corresponding Author) Tel: (0391) 5234003, Fax: (0391) 5225902, E-mail: alishamsy@gmail.com [3] - Assistant Prof., Neuroscience Rasearch Center, University of Medical Sciences, Kerman, Iran [4] - Prof., Dept. of Physiology and Pharmacology, Medical School, University of Medical Sciences, Kerman, Iran [5] - Assistant Prof., Dept. of Physiology and Pharmacology, Medical School, University of Medical Sciences, Rafsanjan, Iran [6] - Associate Prof., Dept. of Biochemistry, University of Medical Sciences, Rafsanjan, Iran