Stevia Extract and MK-801 Attenuate Nalbuphine Tolerance and Dependence in Mice: Role of Glutamate, Nitric Oxide, and Oxidative stress | ||||
| Sphinx Journal of Pharmaceutical and Medical Sciences | ||||
| Volume 6, Issue 1, December 2023, Page 1-14 PDF (1001.66 K) | ||||
| Document Type: Original research articles | ||||
| DOI: 10.21608/sjpms.2023.233910.1022 | ||||
 View on SCiNiTO | ||||
| Author | ||||
Rasha Ali 
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| Pharmacology and Toxicology Department, Faculty of Pharmacy, Sohag University, Sohag, Egypt | ||||
| Abstract | ||||
| This study aimed to investigate for the first time, the potential role of stevia aqueous extract alone and in combination with MK-801 on nalbuphine-induced tolerance and dependence in mice using biochemical and histological tools. In this study, Repeated administration of stevia extract (300 mg/kg, p.o) along with nalbuphine (10 mg/kg, s.c.) attenuated the development of tolerance, as measured by the hot plate test, and dependence, as assessed by naloxone (5 mg/kg, i.p.) - precipitated withdrawal manifestations. Concomitantly, increase in brain glutamate level, malondialdehyde level, and serum nitrite level-induced by repeated administration of nalbuphine to mice or by administration of naloxone to nalbuphine-dependent mice were inhibited by co-administration of stevia extract. Also, co-administration of the stevia extract inhibited the decrease in brain intracellular reduced glutathione level and glutathione peroxidase activity induced by both treatments. The inhibitory effect of the extract on nalbuphine-induced tolerance and dependence and on naloxone-induced biochemical alterations in nalbuphine-dependent mice was enhanced by concurrent i.p. administration of the NMDA receptor antagonist, MK-801 (0.25 mg/kg). histopathological results revealed that stevia extract co-administration produced decrease in nerve cell degeneration, vacuolation, apoptosis and enhance neuropil appearance. This histopathological improvement increased by concurrent administration of MK-801 with stevia extract. These results provide evidence that stevia extract appears to have a therapeutic potential in opioid tolerance and dependence, through inhibition of nalbuphine-induced elevation in glutamate level, NO overproduction and oxidative stress. | ||||
| Keywords | ||||
| Nalbuphine; Tolerance; Dependence; Stevia; MK-801; Glutamate | ||||
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