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Investigating the effect of atorvastatin on development of morphine tolerance evaluated by Hargreaves test in male rats
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Mohammadreza Shahsavari-Asl   , Hossein Azizi  , Saeed Semnanian * |
| 1Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2Institute for Brain and Cognition, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran |
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Abstract: (12 Views) |
Introduction: Opioids such as morphine are highly effective analgesics; however, their prolonged use is often accompanied by adverse effects such as tolerance, dependence, and addiction. These side effects pose significant limitations on long-term opioid therapy. Considering the critical need for better pain management, identifying strategies to slow the development of morphine tolerance is essential. Neuroinflammation is a known contributor to opioid tolerance, and recent evidence suggests that statins, exert anti-inflammatory effects within the central nervous system. This study aimed to investigate whether atorvastatin influences the development of morphine tolerance in male rats.
Methods: Male rats received intraperitoneal morphine (10 mg/kg, twice daily) for seven days in order to induce tolerance. Also, to investigate the effect of atorvastatin on the development of morphine tolerance, rats received atorvastatin (1& 5 mg/kg, once a day) about one hour before morphine injection. Hargreaves test was used on alternate days to assess changes in morphine-induced analgesia.
Results: Behavioral assessment using the paw withdrawal test revealed that chronic administration of atorvastatin at both 1 mg/kg and 5 mg/kg doses prior to each morphine exposure significantly attenuated the development of tolerance to the analgesic effects of morphine. Notably, the 5 mg/kg dose of atorvastatin also significantly maintained a higher percentage of maximum possible analgesic effect on day seven, whereas no significant difference was observed on this day between the atorvastatin 1 + morphine group and the morphine + saline group.
Conclusion: The results indicate that administration of atorvastatin prior to morphine exposure slows the development of tolerance to the analgesic effects of morphine. This effect of atorvastatin may be attributed to its ability to prevent inflammation induced by repeated morphine use. These findings suggest the potential role of statins as adjuvant agents in enhancing the analgesic efficacy of morphine.
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| Keywords: Morphine tolerance, Atorvastatin, Hargreaves test, Rat |
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Full-Text [PDF 951 kb]
(4 Downloads)
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Type of Study: Original Research |
Subject:
Neuroscience
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