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:: Volume 24, Issue 3 (10-2022) ::
J Gorgan Univ Med Sci 2022, 24(3): 41-50 Back to browse issues page
Effects of Lithium on Morphine Tolerance Using Analgesia, Nitrite Determination, Histology and Immunohistochemistry of Forehead Cortex in Adult Male Swiss Mice
Saman Barzegar1 , Tayebeh Noori2 , Mohammad Hosein Farzaei3 , Mozafar Khazaei4 , Samira Shirooie * 5
1- Pharm.D Student, Student Research Committee, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
2- M.Sc in Applied Chemistry, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
3- Associate Professor, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4- Professor, Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
5- Assistant Professor, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. , shirooie@gmail.com
Abstract:   (2673 Views)
Background and Objective: Chronic use of opioids leads to analgesic tolerance. Protein kinase C (PKC), adenylyl cyclase (AC), nitric oxide (NO) and glycogen synthase kinase 3 beta (GSK-3β) are involved in morphine tolerance. Lithium activates the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway that inhibits GSK-3β and reduces morphine-induced tolerance. This study was performed to evaluate the effects of lithium on morphine dependence symptoms and tolerance of its analgesic effects in Swiss mice by GSK-3β signaling.
Methods: This experimental study was performed on 56 Swiss male albino mice that were randomly allocated into 8 groups (each containing 7 mice). The intraperitoneal injection of morphine at different concentrations (50, 50 and 75 mg/kg) and different hours (08:00, 11:00 and 16:00, respectively) was performed for 4 days, and a single dose 50 mg/kg was administered on the 5th day. The effects of three doses of lithium (1, 5 and 10 mg/kg) given orally, 45 min before morphine injections on morphine-induced analgesic tolerance were evaluated. To evaluate analgesia latency on day 1, 3 and 5, tail flick and hot plate tests were done. The brain of each animal was removed to measure nitrite levels, and histological evaluation and immunohistochemistry for p-glycogen synthase (p-GSSer640) were performed on the last day of the study.
Results: Co-administration of lithium significantly increased the latency of analgesia in comparison with the morphine group on the 3rd and 5th day (P<0.05). Lithium reduced the morphine-induced increase of nitrite levels and also reduced brain damage. In addition, immunohistochemistry assay of p-GSSer640 indicated a significant reduction of the morphine-induced phosphorylation of GS at S640 by GSK in the lithium-treated mice.
Conclusion: Lithium administration can reduce morphine tolerance in adult male Swiss mice.
Keywords: Opioid [MeSH], Pain [MeSH], Morphine [MeSH], Glycogen Synthase Kinase 3 beta [MeSH], Lithium [MeSH]
Article ID: Vol24-34
Full-Text [PDF 1363 kb]   (9106 Downloads)    
Type of Study: Original Articles | Subject: Pharmacology
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Barzegar S, Noori T, Farzaei M H, Khazaei M, Shirooie S. Effects of Lithium on Morphine Tolerance Using Analgesia, Nitrite Determination, Histology and Immunohistochemistry of Forehead Cortex in Adult Male Swiss Mice. J Gorgan Univ Med Sci 2022; 24 (3) :41-50
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Volume 24, Issue 3 (10-2022) Back to browse issues page
مجله دانشگاه علوم پزشکی گرگان Journal of Gorgan University of Medical Sciences
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