Chronic Morphine Preconditioning: Interaction of mTOR and iNOS in protection against Ischemia/Reperfusion injury

Document Type : Research article


1 Rajaie Cardiovascular, Medical, and Research Centre, Iran University of Medical Sciences, Tehran, Iran

2 Physiology Research Center, Physiology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

3 Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Neuroscience and Brain Technologies-Istituto Italiano di Technologia,Via Morego, 30, 16163 Genova, Italy


Chronic morphine (CM) treatment increases the phosphorylation of the mammalian target of rapamycin (mTOR), which confers neuroprotection against ischemia/reperfusion (I/R) injury. Besides its important regulatory role in the proliferation, metabolism, and survival of cells, the mTOR is critically involved in intracellular signaling events during I/R injury. In the present study, we investigated the interaction between the expressions of the mTOR and inducible nitric oxide synthase (iNOS) and their possible protective effects on hippocampal neurons against I/R injury in morphine-dependent mice. Additive doses of morphine were administered for 5 days to BALB/c mice so as to induce CM preconditioning before I/R injury. Global brain ischemia was induced via the occlusion of bilateral common carotid arteries for 30 minutes. CM attenuated iNOS expression, NO production, and malondialdehyde activity in the hippocampal tissue. Pretreatment with rapamycin, the mTOR inhibitor, abolished all the above mentioned effects of CM. These findings suggested that CM acted through the mTOR signaling pathways to regulate iNOS expression and oxidative state in the hippocampal tissue after I/R injury.


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