Brain-derived neurotrophic factor (BDNF) is a critical regulator of neuronal survival, synaptic plasticity, and cognitive function, making it a key biomarker in understanding the neurobiological impact of opioid exposure. This study investigated the effects of opioids (codeine and tramadol) on brain-derived neurotrophic factor (BDNF) levels in male Wistar rats. A total of 75 male Wistar rats (120-140g) were used for the study in acute, sub-chronic and chronic phases, using 25 rats for each phase. In each phase, 25 male Wistar rats were divided into 5 groups of 5 animals each. Group 1 served as the control and received distilled water, groups 2 and 3 were treated with tramadol at 20 and 60 mg/kg, respectively, while groups 4 and 5 were supplemented with codeine at 10 and 30 mg/kg, respectively. Treatment by oral gavage lasted for 14, 28 and 56 days for the acute, sub-chronic and chronic studies, respectively. Serum and hippocampal BDNF assays were analysed following standard laboratory protocols. Results showed dose and time-dependent significant reductions (p < 0.05) in BDNF levels across all treatment groups compared to controls, with the most pronounced decreases observed in codeine 30mg/kg and tramadol 60mg/kg groups. These findings suggest that prolonged opioid exposure disrupts neurotrophic signalling, potentially contributing to neurodegenerative conditions.
| Published in | Biomedical Sciences (Volume 12, Issue 1) |
| DOI | 10.11648/j.bs.20261201.12 |
| Page(s) | 10-16 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2026. Published by Science Publishing Group |
Brain-derived Neurotrophic Factor (BDNF), Opioids, Neurodegenerative Conditions
| [1] | Koch C. The Brain: Neurons, Synapses, and Neural Networks. Encyclopedia of Religious Psychology and Behavior: Springer; 2025: 1-4. |
| [2] | Maldonado KA, Alsayouri K. Physiology, brain. StatPearls [Internet]: StatPearls Publishing; 2023. |
| [3] | Lom B. A Review of Developmental Neurobiology by Lynne M. Bianchi (in the Context of One Instructor’s Evolving Relationship with Scientific Textbooks). Journal of Undergraduate Neuroscience Education. 2018; 17(1): R1. |
| [4] | Purves D, Augustine GJ, Fitzpatrick D, Katz L, LaMantia A-S, McNamara JO, Williams SM. Neuroscience. 2nd ed. Sunderland (MA): Sinauer Associates; 2001. |
| [5] | Park H, Poo M-m. Neurotrophin regulation of neural circuit development and function. Nature Reviews Neuroscience. 2013; 14(1): 7-23. |
| [6] | Wang Y, Liang J, Xu B, Yang J, Wu Z, Cheng L. TrkB/BDNF signaling pathway and its small molecular agonists in CNS injury. Life Sciences. 2024; 336: 122282. |
| [7] | Dhaliwal A, Gupta M. Physiology, opioid receptor. 2019. |
| [8] | Sharma B, Bruner A, Barnett G, Fishman M. Opioid use disorders. Child and adolescent psychiatric clinics of North America. 2016; 25(3): 473. |
| [9] | Pergolizzi Jr JV, Raffa RB, Rosenblatt MH. Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management. Journal of clinical pharmacy and therapeutics. 2020; 45(5): 892-903. |
| [10] | Kosciuczuk U, Jakubow P, Czyzewska J, Knapp P, Rynkiewicz-Szczepanska E. Plasma brain-derived neurotrophic factor and opioid therapy: Results of Pilot Cross-Sectional Study. Clinical Medicine & Research. 2022; 20(4): 195-203. |
| [11] | Listos J, Łupina M, Talarek S, Mazur A, Orzelska-Górka J, Kotlińska J. The mechanisms involved in morphine addiction: an overview. International journal of molecular sciences. 2019; 20(17): 4302. |
| [12] | Fricchione GL, Mendoza A, Stefano GB. Morphine and its psychiatric implications. Advances in neuroimmunology. 1994; 4(2): 117-31. |
| [13] | Milella MS, D’Ottavio G, De Pirro S, Barra M, Caprioli D, Badiani A. Heroin and its metabolites: relevance to heroin use disorder. Translational psychiatry. 2023; 13(1): 120. |
| [14] | Tolomeo S, Steele JD, Ekhtiari H, Baldacchino A. Chronic heroin use disorder and the brain: Current evidence and future implications. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2021; 111: 110148. |
| [15] | Wang T-Y, Lee S-Y, Chang Y-H, Chen S-L, Chen PS, Chu C-H, et al. Correlation of cytokines, BDNF levels, and memory function in patients with opioid use disorder undergoing methadone maintenance treatment. Drug and alcohol dependence. 2018; 191: 6-13. |
| [16] | Chikezie UE, Ebuenyi ID. Tramadol misuse in the Niger Delta; A review of cases presenting within a year. Journal of Substance use. 2019; 24(5): 487-91. |
| [17] | Badewo OJ. Knowledge, Perception, Prevalence And Contributing factors to abuse of opioids among students of polytechnic of Ibadan, Ibadan, Oyo State; 2021. Journal of Education, Society and Behavioural Science 2023; 36(10) 93-101. |
| [18] | Ohaju-Obodo JO, Omatighene EO, Okine D, Ayikimi L. Tramadol abuse: A case report. International Journal of Forensic Medical Investigation. 2019; 5(2): 52-8. |
| [19] | Chinko BC, Precious-Abraham AD. Wound healing activity of hydromethanolic Dioscorea bulbifera extract on male wistar rat excision wound models. Pharmacological Research-Modern Chinese Medicine. 2024; 11: 100425. |
| [20] | Daubry TME, Adienbo OM, Ovili-Odili BZ, Chinko BC. N-Acetyl Cysteine and Zinc Sulfate Attenuates Acute Crude Oil-Induced Oxidative Stress and Testicular Structural Damage in Male Wistar Rats. Asian Journal of Biology. 2024; 20(11): 98-108. |
| [21] | Albus U. Guide for the care and use of laboratory animals (8th edn). SAGE Publications Sage UK: London, England; 2012. |
| [22] | National Research Council. Institute for Laboratory Animal Research: Guide for the care and use of laboratory animals. 2010. The National Academies Press. Washington D. C. |
| [23] | Akbarian S, Rios M, Liu R-J, Gold SJ, Fong H-F, Zeiler S, et al. Brain-derived neurotrophic factor is essential for opiate-induced plasticity of noradrenergic neurons. Journal of Neuroscience. 2002; 22(10): 4153-62. |
| [24] | Bachis A, Campbell LA, Jenkins K, Wenzel E, Mocchetti I. Morphine withdrawal increases brain-derived neurotrophic factor precursor. Neurotoxicity research. 2017; 32(3): 509-17. |
| [25] | Ishola I, Eneanya S, Folarin O, Awogbindin I, Abosi A, Olopade J, Okubadejo N. Tramadol and codeine stacking/boosting dose exposure induced neurotoxic behaviors, oxidative stress, mitochondrial dysfunction, and neurotoxic genes in adolescent mice. Neurotoxicity research. 2022; 40(5): 1304-21. |
| [26] | Ezi S, Boroujeni ME, Khatmi A, Vakili K, Fathi M, Abdollahifar M-A, et al. Chronic exposure to tramadol induces neurodegeneration in the cerebellum of adult male rats. Neurotoxicity research. 2021; 39(4): 1134-47. |
| [27] | Chen S-D, Wu C-L, Hwang W-C, Yang D-I. More insight into BDNF against neurodegeneration: anti-apoptosis, anti-oxidation, and suppression of autophagy. International journal of molecular sciences. 2017; 18(3): 545. |
| [28] | Mitrovic M, Selakovic D, Jovicic N, Ljujic B, Rosic G. BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2025; 26(10): 4926. |
| [29] | Vašková J, Kočan L, Vaško L. Oxidative stress and opioids. Glob J Anesth. 2016; 3(1): 020-9. |
| [30] | Rozisky J, Laste G, De Macedo I, Santos V, Krolow R, Noschang C, et al. Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats. Neurochemical research. 2013; 38(3): 494-503. |
| [31] | Bennett MT, Modna Y, Shah DK. The Impact of Opioid Drugs on Memory and Other Cognitive Functions: A Review. Journal of Biosciences and Medicines. 2024; 12(4): 264-87. |
| [32] | Pignolo RJ. Opioids and Accelerated Brain Aging: The White Matter Matters. Mayo Clinic Proceedings, 2024. Elsevier: 691-2. |
APA Style
Krukru, E. E., Chinko, B. C., Dapper, V. D. (2026). Opioid-Induced Dysregulation of BDNF Signalling: A Study of Acute, Sub-Chronic, and Chronic Exposure in a Rodent Model. Biomedical Sciences, 12(1), 10-16. https://doi.org/10.11648/j.bs.20261201.12
ACS Style
Krukru, E. E.; Chinko, B. C.; Dapper, V. D. Opioid-Induced Dysregulation of BDNF Signalling: A Study of Acute, Sub-Chronic, and Chronic Exposure in a Rodent Model. Biomed. Sci. 2026, 12(1), 10-16. doi: 10.11648/j.bs.20261201.12
@article{10.11648/j.bs.20261201.12,
author = {Elizabeth Eepho Krukru and Bruno Chukwuemeka Chinko and Victor Datonye Dapper},
title = {Opioid-Induced Dysregulation of BDNF Signalling: A Study of Acute, Sub-Chronic, and Chronic Exposure in a Rodent Model},
journal = {Biomedical Sciences},
volume = {12},
number = {1},
pages = {10-16},
doi = {10.11648/j.bs.20261201.12},
url = {https://doi.org/10.11648/j.bs.20261201.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.bs.20261201.12},
abstract = {Brain-derived neurotrophic factor (BDNF) is a critical regulator of neuronal survival, synaptic plasticity, and cognitive function, making it a key biomarker in understanding the neurobiological impact of opioid exposure. This study investigated the effects of opioids (codeine and tramadol) on brain-derived neurotrophic factor (BDNF) levels in male Wistar rats. A total of 75 male Wistar rats (120-140g) were used for the study in acute, sub-chronic and chronic phases, using 25 rats for each phase. In each phase, 25 male Wistar rats were divided into 5 groups of 5 animals each. Group 1 served as the control and received distilled water, groups 2 and 3 were treated with tramadol at 20 and 60 mg/kg, respectively, while groups 4 and 5 were supplemented with codeine at 10 and 30 mg/kg, respectively. Treatment by oral gavage lasted for 14, 28 and 56 days for the acute, sub-chronic and chronic studies, respectively. Serum and hippocampal BDNF assays were analysed following standard laboratory protocols. Results showed dose and time-dependent significant reductions (p < 0.05) in BDNF levels across all treatment groups compared to controls, with the most pronounced decreases observed in codeine 30mg/kg and tramadol 60mg/kg groups. These findings suggest that prolonged opioid exposure disrupts neurotrophic signalling, potentially contributing to neurodegenerative conditions.},
year = {2026}
}
TY - JOUR T1 - Opioid-Induced Dysregulation of BDNF Signalling: A Study of Acute, Sub-Chronic, and Chronic Exposure in a Rodent Model AU - Elizabeth Eepho Krukru AU - Bruno Chukwuemeka Chinko AU - Victor Datonye Dapper Y1 - 2026/02/21 PY - 2026 N1 - https://doi.org/10.11648/j.bs.20261201.12 DO - 10.11648/j.bs.20261201.12 T2 - Biomedical Sciences JF - Biomedical Sciences JO - Biomedical Sciences SP - 10 EP - 16 PB - Science Publishing Group SN - 2575-3932 UR - https://doi.org/10.11648/j.bs.20261201.12 AB - Brain-derived neurotrophic factor (BDNF) is a critical regulator of neuronal survival, synaptic plasticity, and cognitive function, making it a key biomarker in understanding the neurobiological impact of opioid exposure. This study investigated the effects of opioids (codeine and tramadol) on brain-derived neurotrophic factor (BDNF) levels in male Wistar rats. A total of 75 male Wistar rats (120-140g) were used for the study in acute, sub-chronic and chronic phases, using 25 rats for each phase. In each phase, 25 male Wistar rats were divided into 5 groups of 5 animals each. Group 1 served as the control and received distilled water, groups 2 and 3 were treated with tramadol at 20 and 60 mg/kg, respectively, while groups 4 and 5 were supplemented with codeine at 10 and 30 mg/kg, respectively. Treatment by oral gavage lasted for 14, 28 and 56 days for the acute, sub-chronic and chronic studies, respectively. Serum and hippocampal BDNF assays were analysed following standard laboratory protocols. Results showed dose and time-dependent significant reductions (p < 0.05) in BDNF levels across all treatment groups compared to controls, with the most pronounced decreases observed in codeine 30mg/kg and tramadol 60mg/kg groups. These findings suggest that prolonged opioid exposure disrupts neurotrophic signalling, potentially contributing to neurodegenerative conditions. VL - 12 IS - 1 ER -