Ashwagandha enhances behavior and brain neurotransmitters in Tramadol treated and withdrawal rats | ||||
| Egyptian Pharmaceutical Journal | ||||
| Article 10, Volume 24, Issue 3, July 2025, Page 98-114 PDF (1.28 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/epj.2025.374982.1080 | ||||
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| Authors | ||||
Shimaa S. H. Ahmed1; Nadia M.S. Arafa2; Hoda G.S. Hegazy1; Elham HA Ali  3
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| 1Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt. | ||||
| 2Physiology Department, Egyptian Drug Authority (EDA), Cairo, Egypt | ||||
| 3Asma Fahmy St., PO Box 11586, Nasr City, Cairo, Egypt | ||||
| Abstract | ||||
| Background Although tramadol (TRE) was designed to be a safer alternative to more potent prescription analgesics, TRE abuse raises the risk of its toxic consequences on the brain. Objective The present study aims to reveal the defensive outcome of Withania somnifera (ASH), an adaptogen plant with antioxidant performance, on the TRE misuse side-effects in the cortex and brainstem neurotransmitters and behavior and hippocampus cytokines. Materials and methods The rats were divided into two main groups. The treatment group (A) was divided into control, ASH (200 mg/kg), TRE (40 mg/kg) and TRE+ASH treated with the same doses for six weeks. The withdrawal group (B) treated for ten weeks, and was divided into control, ASH was treated with vehicle for six weeks before being treated with 200 mg/kg for the next four weeks. TRE was treated by successive doses every two weeks (40, 80, 120 mg/kg) for the first six weeks before being treated by vehicle for the next four weeks, and TRE+ASH received the same ASH and TRE doses as the ASH and TRE groups. All the groups were treated daily p.o. The open-field and Y mazes were performed before the end of the experiment. After decapitation, the cortex and brainstem AChE activity were detected calorimetrically, and neurotransmitters were detected by HPLC technique. Also, hippocampus TNF-α and IL-1β contents were assessed by IHC. Results and conclusion The TRE+ASH groups showed a significant improvement in open fields and Y maze tasks after the adverse effects of TRE treatment. Also, an improvement in the cortex and brainstem neurotransmitter contents (glutamate, aspartate, gamma amino butyric acid, glycine, norepinephrine, dopamine, serotonin, and β-endorphin) in TRE+ASH groups compared with the TRE groups. Furthermore, ASH reduced the elevated acetylcholinesterase and hippocampal TNF-α and IL-1β contents that were elevated in TRE treated groups. In conclusion, ASH owns a valuable neurotherapeutic impact through modulation of different neurotransmitters and suppression of proinflammatory cytokines, which reflected on the behavior of the treated rats. | ||||
| Keywords | ||||
| brain; neurotransmitters; behavior; proinflammatory cytokines | ||||
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