1. Valipour R, Shekari A, Setareh M. Identification of medicine
components in herbal drugs for addiction treatment; a case
study of Zanjan city. Iran J Forensic Med. 2019;25(1):61-4.
2. Aghajanpour F, Eskandarian Boroujeni M, Jahanian A, Soltani
R, Ezi S, Khatmi A, et al. Tramadol: a potential neurotoxic
agent affecting prefrontal cortices in adult male rats and PC12 cell line. Neurotox Res. 2020;38(2):385-97. doi: 10.1007/
s12640-020-00214-z.
3. Ezi S, Eskandarian Boroujeni M, Khatmi A, Vakili K, Fathi M,
Abdollahifar MA, et al. Chronic exposure to tramadol induces
neurodegeneration in the cerebellum of adult male rats.
Neurotox Res. 2021;39(4):1134-47. doi: 10.1007/s12640-
021-00354-w.
4. Subedi M, Bajaj S, Kumar MS, Yc M. An overview of tramadol
and its usage in pain management and future perspective.
Biomed Pharmacother. 2019;111:443-51. doi: 10.1016/j.
biopha.2018.12.085.
5. Khatmi A, Eskandarian Boroujeni M, Ezi S, Mirbehbahani
SH, Aghajanpour F, Soltani R, et al. Combined molecular,
structural and memory data unravel the destructive effect of
tramadol on hippocampus. Neurosci Lett. 2022;771:136418.
doi: 10.1016/j.neulet.2021.136418.
6. Vazzana M, Andreani T, Fangueiro J, Faggio C, Silva C,Santini A, et al. Tramadol hydrochloride: pharmacokinetics,
pharmacodynamics, adverse side effects, co-administration of
drugs and new drug delivery systems. Biomed Pharmacother.
2015;70:234-8. doi: 10.1016/j.biopha.2015.01.022.
7. Lavasani H, Sheikholeslami B, Hosseinzadeh Ardakani
Y, Abdollahi M, Hakemi L, Rouini MR. Study of the
pharmacokinetic changes of tramadol in diabetic rats. Daru.
2013;21(1):17. doi: 10.1186/2008-2231-21-17 .
8. Eassa BI, El-Shazly MA. Safety and efficacy of tramadol
hydrochloride on treatment of premature ejaculation. Asian J
Androl. 2013;15(1):138-42. doi: 10.1038/aja.2012.96.
9. Ali OK, Ahmed AJ, Mawlood AG. Effects of tramadol on
histopathological and biochemical parameters in male rabbits.
Am J Biol Life Sci. 2015;3(3):85-90.
10. Edinoff AN, Kaplan LA, Khan S, Petersen M, Sauce E,
Causey CD, et al. Full Opioid Agonists and Tramadol:
Pharmacological and Clinical Considerations. Anesth Pain
Med 2021;11(4):e119156. doi: 10.5812/aapm.119156.
11. Lee SH, Cho SY, Lee HG, Choi JI, Yoon MH, Kim WM.
Tramadol induced paradoxical hyperalgesia. Pain Physician.
2013;16(1):41-4.
12. Callaghan CK, Rouine J, O’Mara SM. Potential roles for
opioid receptors in motivation and major depressive
disorder. Prog Brain Res. 2018;239:89-119. doi: 10.1016/
bs.pbr.2018.07.009.
13. Hussein OA, Abdel Mola AF, Rateb A. Tramadol administration
induced hippocampal cells apoptosis, astrogliosis, and
microgliosis in juvenile and adult male mice, histological
and immunohistochemical study. Ultrastruct Pathol.
2020;44(1):81-102. doi: 10.1080/01913123.2019.1711480.
14. Abdel-Hamid IA, Andersson KE, Waldinger MD, Anis
TH. Tramadol abuse and sexual function. Sex Med Rev.
2016;4(3):235-46. doi: 10.1016/j.sxmr.2015.10.014.
15. Nafea OE, ElKhishin IA, Awad OA, Mohamed DA. A study of
the neurotoxic effects of tramadol and cannabis in adolescent
male albino rats. Int J Sci Rep. 2016;2(7):143-54. doi:
10.18203/issn.2454-2156.IntJSciRep20162164.
16. Ahmed AI, El-Dawy K, Fawzy MM, Abdallah HA, Elsaid HN,
Elmesslamy WO. Retrospective review of tramadol abuse.
Slov Vet Res. 2018;55(Suppl 20):471-83. doi: 10.26873/svr677-2018.
17. Zebedee LU, Bariweni MW, Oboma YI, Ilegbedion IG.
Tramadol abuse and addiction: effects on learning, memory,
and organ damage. Egypt Pharm J. 2022;21(1):75-83.
18. Soltani R, Eskandarian Boroujeni M, Aghajanpour F, Khatmi A,
Ezi S, Mirbehbahani SH, et al. Tramadol exposure upregulated
apoptosis, inflammation and autophagy in PC12 cells and rat’s
striatum: an in vitro- in vivo approach. J Chem Neuroanat.
2020;109:101820. doi: 10.1016/j.jchemneu.2020.101820.
19. Stoops WW, Lofwall MR, Nuzzo PA, Craig LB, Siegel AJ,
Walsh SL. Pharmacodynamic profile of tramadol in humans:
influence of naltrexone pretreatment. Psychopharmacology
(Berl). 2012;223(4):427-38. doi: 10.1007/s00213-012-2739-4.
20. Nakhaee S, Hoyte C, Dart RC, Askari M, Lamarine RJ,
Mehrpour O. A review on tramadol toxicity: mechanism of
action, clinical presentation, and treatment. Forensic Toxicol.
2021;39(2):293-310. doi: 10.1007/s11419-020-00569-0 .
21. Omar NM. Nigella sativa oil alleviates ultrastructural
alterations induced by tramadol in rat motor cerebral cortex.
J Microsc Ultrastruct. 2016;4(2):76-84. doi: 10.1016/j.
jmau.2015.12.001.
22. Imanpour V, Reisi P. The effect of orexin-2 and
endocannabinoid-1 antagonists on neuronal activity of
hippocampal CA1 pyramidal neurons in response to tramadol
in rats. Adv Biomed Res. 2022;11:26. doi: 10.4103/abr.
abr_65_21.
23. Rahimi HR, Soltaninejad K, Shadnia S. Acute tramadol
poisoning and its clinical and laboratory findings. J Res Med
Sci. 2014;19(9):855-9.
24. Dhagudu NK, Erravalli A, Sarkar S, Chadda RK. Tramadolrelated adverse drug reactions at an addiction psychiatry
setting: a cross-sectional analysis. Indian J Psychol Med.
2019;41(6):593-5. doi: 10.4103/ijpsym.ijpsym_330_18.
25. Mohammadnejad L, Soltaninejad K. Tramadol-induced organ
toxicity via oxidative stress: a review study. Int J Med Toxicol
Forensic Med. 2022;12(1):35430. doi: 10.32598/ijmtfm.
v12i1.35430.
26. Elkhateeb A, El Khishin I, Megahed O, Mazen F. Effect of
Nigella sativa Linn oil on tramadol-induced hepato- and
nephrotoxicity in adult male albino rats. Toxicol Rep.
2015;2:512-9. doi: 10.1016/j.toxrep.2015.03.002.
27. Lagard C, Chevillard L, Malissin I, Risède P, Callebert J, Labat
L, et al. Mechanisms of tramadol-related neurotoxicity in the
rat: does diazepam/tramadol combination play a worsening
role in overdose? Toxicol Appl Pharmacol. 2016;310:108-19.
doi: 10.1016/j.taap.2016.09.013.
28. Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A,
Abdollahi M, Dart RC. Factors related to seizure in tramadol
poisoning and its blood concentration. J Med Toxicol.
2011;7(3):183-8. doi: 10.1007/s13181-011-0168-0.
29. Kose EA, Bakar B, Ayva SK, Kilinc K, Apan A. Effects of
intracisternal tramadol on cerebral and spinal neuronal cells
in rat. Minerva Anestesiol. 2014;80(8):904-12.
30. Ragab IK, Mohamed HZ. Histological changes of the adult
albino rats entorhinal cortex under the effect of tramadol
administration: histological and morphometric study. Alex J
Med. 2017;53(2):123-33. doi: 10.1016/j.ajme.2016.05.001.
31. Atici S, Cinel L, Cinel I, Doruk N, Aktekin M, Akca A, et al.
Opioid neurotoxicity: comparison of morphine and tramadol in
an experimental rat model. Int J Neurosci. 2004;114(8):1001-
11. doi: 10.1080/00207450490461314.
32. Fathy H, Yassa H, Almaz D, Mohamed R. Acute and subchronic
tramadol toxicity on brain and spinal cord of male albino rats.
Ain Shams J Forensic Med Clin Toxicol. 2013;20(1):135-45.
doi: 10.21608/ajfm.2013.19397.
33. Cherner M, Suarez P, Casey C, Deiss R, Letendre S, Marcotte
T, et al. Methamphetamine use parameters do not predict
neuropsychological impairment in currently abstinent
dependent adults. Drug Alcohol Depend. 2010;106(2-3):154-
63. doi: 10.1016/j.drugalcdep.2009.08.010.
34. Zakaryaee H, Mollazadeh J, Aflakseir A, Khormaei F, Soofi
A. Cognitive impairment in methamphetamine buprenorphin
and tramadol users. Eur J Sci Res. 2012;68(3):321-7.
35. Niknamfar S, Nouri Zadeh-Tehrani S, Sadat-Shirazi MS,
Akbarabadi A, Rahimi-Movaghar A, Zarrindast MR. μ-Opioid
receptor in the CA1 involves in tramadol and morphine cross
state-dependent memory. Neurosci Lett. 2019;705:177-82.
doi: 10.1016/j.neulet.2019.04.054.
36. Song D, Wang D, Yang Q, Yan T, Wang Z, Yan Y, et al. The
lateralization of left hippocampal CA3 during the retrieval of
spatial working memory. Nat Commun. 2020;11(1):2901.
doi: 10.1038/s41467-020-16698-4.
37. Umbach G, Kantak P, Jacobs J, Kahana M, Pfeiffer BE, Sperling
M, et al. Time cells in the human hippocampus and entorhinal
cortex support episodic memory. Proc Natl Acad Sci U S A.
2020;117(45):28463-74. doi: 10.1073/pnas.2013250117.
38. Vafaei-Nezhad S, Hami J, Sadeghi A, Ghaemi K, Hosseini M,
Abedini MR, et al. The impacts of diabetes in pregnancy on
hippocampal synaptogenesis in rat neonates. Neuroscience.
2016;318:122-33. doi: 10.1016/j.neuroscience.2016.01.025.
39. Vafaei-Nezhad S, Vafaei-Nezhad M, Shadi M, Ezi S. The
impact of diabetes on hippocampus. In: Zhang X, ed.Hippocampus-Cytoarchitecture and Diseases. IntechOpen;
2021. doi: 10.5772/intechopen.99895.
40. Hami J, Shojae F, Vafaee-Nezhad S, Lotfi N, Kheradmand H,
Haghir H. Some of the experimental and clinical aspects of the
effects of the maternal diabetes on developing hippocampus.
World J Diabetes. 2015;6(3):412-22. doi: 10.4239/wjd.
v6.i3.412.
41. Alam MJ, Kitamura T, Saitoh Y, Ohkawa N, Kondo T, Inokuchi
K. Adult neurogenesis conserves hippocampal memory
capacity. J Neurosci. 2018;38(31):6854-63. doi: 10.1523/
jneurosci.2976-17.2018.
42. Khalifa HE, Darweesh A, Hassaan S, Mostafa S. Assessment
of cognitive functions in tramadol-dependent patients.
Middle East Curr Psychiatr. 2018;25(1):2-5. doi: 10.1097/01.
xme.0000526928.54570.
43. Szkutnik-Fiedler D, Kus K, Ratajczak P, Antoniów M,
Nowakowska E, Grześkowiak E. Coadministration of tramadol
with aripiprazole and venlafaxine--the effect on spatial memory
functions in male rats. Pharmacol Rep. 2016;68(2):451-6. doi:
10.1016/j.pharep.2015.11.003.
44. Bassiony MM, Youssef UM, Hassan MS, Salah El-Deen GM,
El-Gohari H, Abdelghani M, et al. Cognitive impairment
and tramadol dependence. J Clin Psychopharmacol.
2017;37(1):61-6. doi: 10.1097/jcp.0000000000000617.
45. Hassaan SH, Khalifa H, Darwish AM. Effects of extended
abstinence on cognitive functions in tramadol-dependent
patients: a cohort study. Neuropsychopharmacol Rep.
2021;41(3):371-8. doi: 10.1002/npr2.12188.
46. Mahdi S. Attention and memory in tramadol addiction. Sohag
Med J. 2018;22(3):285-9. doi: 10.21608/smj.2018.34496.
47. Elrassas HH, Elsayed YA, El Nagar ZM, Abdeen MS,
Mohamed AT. Cognitive impairment in patients diagnosed
with tramadol dependence compared to healthy controls.
Int Clin Psychopharmacol. 2021;36(1):38-44. doi: 10.1097/
yic.0000000000000340.
48. Ahmadi M, Hoseinzade A, Haghighi S, Yosefi S. Complex
partial seizure and hippocampus atrophy caused by
tramadol abuse: a case study. Ann Mil Health Sci Res.
2017;15(1):e61240. doi: 10.5812/amh.61240.
49. Jafari-Sabet M, Jafari-Sabet AR, Dizaji-Ghadim A. Tramadol
state-dependent memory: involvement of dorsal hippocampal
muscarinic acetylcholine receptors. Behav Pharmacol.
2016;27(5):470-8. doi: 10.1097/fbp.0000000000000239.
50. Sardari M, Rezayof A, Khodagholi F, Zarrindast MR. Basolateral
amygdala GABA-A receptors mediate stress-induced memory
retrieval impairment in rats. Int J Neuropsychopharmacol.
2014;17(4):603-12. doi: 10.1017/s1461145713001363.
51. Hosseini-Sharifabad A, Rabbani M, Sharifzadeh M, Bagheri
N. Acute and chronic tramadol administration impair spatial
memory in rat. Res Pharm Sci. 2016;11(1):49-57.
52. Vago DR, Bevan A, Kesner RP. The role of the direct perforant
path input to the CA1 subregion of the dorsal hippocampus
in memory retention and retrieval. Hippocampus.
2007;17(10):977-87. doi: 10.1002/hipo.20329.
53. Topolnik L, Tamboli S. The role of inhibitory circuits in
hippocampal memory processing. Nat Rev Neurosci.
2022;23(8):476-92. doi: 10.1038/s41583-022-00599-0.
54. Elwy A, Tabl G. Impact of tramadol and morphine abuse on
the activities of acetylcholine esterase, Na+/K+-ATPase and
related parameters in cerebral cortices of male adult rats.
Electron Physician. 2017;9(3):4027-34. doi: 10.19082/4027.
55. Christie MJ. Cellular neuroadaptations to chronic opioids:
tolerance, withdrawal and addiction. Br J Pharmacol.
2008;154(2):384-96. doi: 10.1038/bjp.2008.100.
56. Matthies H, Schroeder H, Becker A, Loh H, Höllt V, Krug M.
Lack of expression of long-term potentiation in the dentate
gyrus but not in the CA1 region of the hippocampus of
mu-opioid receptor-deficient mice. Neuropharmacology.
2000;39(6):952-60. doi: 10.1016/s0028-3908(99)00203-8.
57. Korpi ER, den Hollander B, Farooq U, Vashchinkina E,
Rajkumar R, Nutt DJ, et al. Mechanisms of action and
persistent neuroplasticity by drugs of abuse. Pharmacol Rev.
2015;67(4):872-1004. doi: 10.1124/pr.115.010967.
58. Sivakumar S, Ghasemi M, Schachter SC. Targeting NMDA
receptor complex in management of epilepsy. Pharmaceuticals
(Basel). 2022;15(10):1297. doi: 10.3390/ph15101297.
59. Weiss F, Caruso V, De Rosa U, Beatino MF, Barbuti M,
Nicoletti F, et al. The role of NMDA receptors in bipolar
disorder: a systematic review. Bipolar Disord. 2023;25(8):624-
36. doi: 10.1111/bdi.13335.
60. Jafari-Sabet M, Mofidi H, Attarian-Khosroshahi MS. NMDA
receptors in the dorsal hippocampal area are involved in
tramadol state-dependent memory of passive avoidance
learning in mice. Can J Physiol Pharmacol. 2018;96(1):45-50.
doi: 10.1139/cjpp-2017-0228.
61. Rossato JI, Radiske A, Gonzalez MC, Apolinário G, de Araújo
RLS, Bevilaqua LRM, et al. NMDARs control object recognition
memory destabilization and reconsolidation. Brain Res Bull.
2023;197:42-8. doi: 10.1016/j.brainresbull.2023.03.013.
62. Ledo A, Frade J, Barbosa RM, Laranjinha J. Nitric oxide in
brain: diffusion, targets and concentration dynamics in
hippocampal subregions. Mol Aspects Med. 2004;25(1-2):75-
89. doi: 10.1016/j.mam.2004.02.010.
63. Feil R, Kleppisch T. NO/cGMP-dependent modulation of
synaptic transmission. Handb Exp Pharmacol. 2008(184):529-
60. doi: 10.1007/978-3-540-74805-2_16.
64. Jafari-Sabet M, Amiri S, Ataee R. Cross state-dependency of
learning between tramadol and MK-801 in the mouse dorsal
hippocampus: involvement of nitric oxide (NO) signaling
pathway. Psychopharmacology (Berl). 2018;235(7):1987-99.
doi: 10.1007/s00213-018-4897-5.
65. Jafari-Sabet M. NMDA receptor blockers prevents the
facilitatory effects of post-training intra-dorsal hippocampal
NMDA and physostigmine on memory retention of passive
avoidance learning in rats. Behav Brain Res. 2006;169(1):120-
7. doi: 10.1016/j.bbr.2005.12.011.
66. Berrocoso E, Micó JA, Ugedo L. In vivo effect of tramadol on
locus coeruleus neurons is mediated by alpha2-adrenoceptors
and modulated by serotonin. Neuropharmacology.
2006;51(1):146-53. doi: 10.1016/j.neuropharm.2006.03.013.
67. Barber J. Examining the use of tramadol hydrochloride as an
antidepressant. Exp Clin Psychopharmacol. 2011;19(2):123-
30. doi: 10.1037/a0022721.
68. Duman RS, Li N, Liu RJ, Duric V, Aghajanian G. Signaling
pathways underlying the rapid antidepressant actions of
ketamine. Neuropharmacology. 2012;62(1):35-41. doi:
10.1016/j.neuropharm.2011.08.044.
69. Hashimoto K. Role of the mTOR signaling pathway in the
rapid antidepressant action of ketamine. Expert Rev Neurother.
2011;11(1):33-6. doi: 10.1586/ern.10.176.
70. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, et al.
mTOR-dependent synapse formation underlies the rapid
antidepressant effects of NMDA antagonists. Science.
2010;329(5994):959-64. doi: 10.1126/science.1190287.
71. Jernigan CS, Goswami DB, Austin MC, Iyo AH, Chandran
A, Stockmeier CA, et al. The mTOR signaling pathway in
the prefrontal cortex is compromised in major depressive
disorder. Prog Neuropsychopharmacol Biol Psychiatry.
2011;35(7):1774-9. doi: 10.1016/j.pnpbp.2011.05.010.
72. Yang C, Li WY, Yu HY, Gao ZQ, Liu XL, Zhou ZQ, et al.
Tramadol pretreatment enhances ketamine-induced
antidepressant effects and increases mammalian target ofrapamycin in rat hippocampus and prefrontal cortex. J Biomed
Biotechnol. 2012;2012:175619. doi: 10.1155/2012/175619.
73. Yalcin I, Aksu F, Bodard S, Chalon S, Belzung C.
Antidepressant-like effect of tramadol in the unpredictable
chronic mild stress procedure: possible involvement of the
noradrenergic system. Behav Pharmacol. 2007;18(7):623-31.
doi: 10.1097/FBP.0b013e3282eff109.
74. Bloms-Funke P, Dremencov E, Cremers TI, Tzschentke TM.
Tramadol increases extracellular levels of serotonin and
noradrenaline as measured by in vivo microdialysis in the
ventral hippocampus of freely-moving rats. Neurosci Lett.
2011;490(3):191-5. doi: 10.1016/j.neulet.2010.12.049.
75. Baghishani F, Mohammadipour A, Hosseinzadeh H, Hosseini
M, Ebrahimzadeh-Bideskan A. The effects of tramadol
administration on hippocampal cell apoptosis, learning and
memory in adult rats and neuroprotective effects of crocin.
Metab Brain Dis. 2018;33(3):907-16. doi: 10.1007/s11011-
018-0194-6.
76. Elkerdasy HI, Shaheen NF. Histological and
immunohistochemical study on the effect of tramadol
abuse on cerebral cortex and hippocampus in male albino
rabbits. Egypt J Histol. 2020;43(1):75-87. doi: 10.21608/
ejh.2019.10984.1103.
77. Hosseindoost S, Akbarabadi A, Sadat-Shirazi MS, Mousavi
SM, Khalifeh S, Mokri A, et al. Effect of tramadol on apoptosis
and synaptogenesis in hippocampal neurons: the possible role
of µ-opioid receptor. Drug Dev Res. 2022;83(6):1425-33. doi:
10.1002/ddr.21973.
78. Mehdizadeh H, Pourahmad J, Taghizadeh G, Vousooghi N,
Yoonessi A, Naserzadeh P, et al. Mitochondrial impairments
contribute to spatial learning and memory dysfunction
induced by chronic tramadol administration in rat: protective
effect of physical exercise. Prog Neuropsychopharmacol
Biol Psychiatry. 2017;79(Pt B):426-33. doi: 10.1016/j.
pnpbp.2017.07.022.
79. Ahmadian-Moghadam H, Sadat-Shirazi MS, Azmoun S,
Vafadoost R, Khalifeh S, Zarrindast MR. Tramadol treatment
induces change in phospho-cyclic adenosine monophosphate
response element-binding protein and delta and mu opioid
receptors within hippocampus and amygdala areas of rat
brain. Addict Health. 2021;13(3):165-75. doi: 10.22122/ahj.
v13i3.306.
80. Ali HA, Afifi M, Saber TM, Makki AA, Keshta AT, Baeshen
M, et al. Neurotoxic, hepatotoxic and nephrotoxic
effects of tramadol administration in rats. J Mol Neurosci.
2020;70(12):1934-42. doi: 10.1007/s12031-020-01592-x.
81. Valian N, Sorayya M, Asadi S, Sherafati F, Ershad A,
Savaheli S, et al. Preconditioning by ultra-low dose of
tramadol reduces the severity of tramadol-induced seizure:
contribution of glutamate receptors. Biomed Pharmacother.
2021;133:111031. doi: 10.1016/j.biopha.2020.111031.
82. Sadek KM, Lebda MA, Abouzed TK, Nasr SM, El-Sayed Y.
The molecular and biochemical insight view of lycopene in
ameliorating tramadol-induced liver toxicity in a rat model:
implication of oxidative stress, apoptosis, and MAPK signaling
pathways. Environ Sci Pollut Res Int. 2018;25(33):33119-30.
doi: 10.1007/s11356-018-3265-7.
83. Hakami AY, Alghamdi BS, Alshehri FS. Exploring the potential
use of melatonin as a modulator of tramadol-induced
rewarding effects in rats. Front Pharmacol 2024;15:1373746.
doi: 10.3389/fphar.2024.1373746.
84. Ishola IO, Eneanya SU, Folarin OR, Awogbindin IO, Abosi AJ,
Olopade JO, et al. Tramadol and codeine stacking/boosting
dose exposure induced neurotoxic behaviors, oxidative
stress, mitochondrial dysfunction, and neurotoxic genes in
adolescent mice. Neurotox Res. 2022;40(5):1304-21. doi:
10.1007/s12640-022-00539-x.
85. Mehranpour M, Hassani Moghaddam M, Abdollahifar MA,
Aliaghaei A. Increase Apoptosis, Inflammation, and Oxidative
Stress in the Choroid Plexus of Adult Male Rats by Tramadol
Administration. 2022. Available from: https://ssrn.com/
abstract=4284418.
86. Kamranian H, Asoudeh H, Kamrani Sharif R, Taheri F,
Hayes AW, Gholami M, et al. Neuroprotective potential of
trimetazidine against tramadol-induced neurotoxicity: role of
PI3K/Akt/mTOR signaling pathways. Toxicol Mech Methods.
2023;33(7):607-23. doi: 10.1080/15376516.2023.2202785.
87. Gholami M, Hayes AW, Jamaati H, Sureda A, Motaghinejad
M. Role of apoptosis and autophagy in mediating tramadolinduced neurodegeneration in the rat hippocampus. Mol Biol
Rep. 2023;50(9):7393-404. doi: 10.1007/s11033-023-08641-9.
88. Prado VF, Janickova H, Al-Onaizi MA, Prado MA. Cholinergic
circuits in cognitive flexibility. Neuroscience. 2017;345:130-
41. doi: 10.1016/j.neuroscience.2016.09.013.
89. Logue SF, Gould TJ. The neural and genetic basis of executive
function: attention, cognitive flexibility, and response
inhibition. Pharmacol Biochem Behav. 2014;123:45-54. doi:
10.1016/j.pbb.2013.08.007.
90. Attoh-Mensah E, Léger M, Loggia G, Fréret T, Chavoix C,
Schumann-Bard P. Effects of chronic tramadol administration
on cognitive flexibility in mice. Psychopharmacology (Berl).
2021;238(10):2883-93. doi: 10.1007/s00213-021-05903-x.
91. Said Shalaby A, Mohamed El-Seidy A, Aly Zayed M, Ragab
Allam A. Does tramadol dependence impair cognitive
functions? Int Clin Psychopharmacol. 2022;37(2):67-71. doi:
10.1097/yic.0000000000000389.
92. Khoshsirat S, Abbaszadeh HA, Khoramgah MS, Darabi S,
Mansouri V, Ahmady-Roozbahany N, et al. Protective effect of
photobiomodulation therapy and bone marrow stromal stem
cells conditioned media on pheochromocytoma cell line 12
against oxidative stress induced by hydrogen peroxide. J Lasers
Med Sci. 2019;10(3):163-70. doi: 10.15171/jlms.2019.26.
93. Circu ML, Aw TY. Reactive oxygen species, cellular redox
systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749-
62. doi: 10.1016/j.freeradbiomed.2009.12.022.
94. Poor Hassan M, Abdollahifar MA, Aliaghaei A, Tabeie F,
Vafaei-Nezhad S, Norouzian M, et al. Photobiomodulation
therapy improved functional recovery and overexpression
of interleukins-10 after contusion spinal cord injury in rats.
J Chem Neuroanat. 2021;117:102010. doi: 10.1016/j.
jchemneu.2021.102010.
95. Bameri B, Shaki F, Ahangar N, Ataee R, Samadi M,
Mohammadi H. Evidence for the involvement of the
dopaminergic system in seizure and oxidative damage
induced by tramadol. Int J Toxicol. 2018;37(2):164-70. doi:
10.1177/1091581817753607.
96. Mohamed HM, Mahmoud AM. Chronic exposure to the
opioid tramadol induces oxidative damage, inflammation and
apoptosis, and alters cerebral monoamine neurotransmitters
in rats. Biomed Pharmacother. 2019;110:239-47. doi:
10.1016/j.biopha.2018.11.141.
97. Ali HA, Afifi M, Saber TM, Makki AA, Keshta AT, Baeshen
M, et al. Neurotoxic, hepatotoxic and nephrotoxic
effects of tramadol administration in rats. J Mol Neurosci.
2020;70(12):1934-42. doi: 10.1007/s12031-020-01592-x.
98. Mohamed TM, Ghaffar HM, El Husseiny RM. Effects of tramadol,
clonazepam, and their combination on brain mitochondrial
complexes. Toxicol Ind Health. 2015;31(12):1325-33. doi:
10.1177/0748233713491814.
99. Kamranian H, Asoudeh H, Sharif RK, Taheri F, Hayes AW,
Gholami M, et al. Neuroprotective potential of trimetazidine
against tramadol-induced neurotoxicity: role of PI3K/Akt/mTOR signaling pathways. Toxicol Mech Methods.
2023;33(7):607-23. doi: 10.1080/15376516.2023.2202785.
100. Shabani M, Jamali Z, Naserian A, Khezri S, Salimi A.
Maintenance of mitochondrial function by sinapic acid
protects against tramadol-induced toxicity in isolated
mitochondria obtained from rat brain. Naunyn Schmiedebergs
Arch Pharmacol. 2024;397(2):889-97. doi: 10.1007/s00210-
023-02648-6.
101. Kwon HS, Koh SH. Neuroinflammation in neurodegenerative
disorders: the roles of microglia and astrocytes. Transl
Neurodegener. 2020;9(1):42. doi: 10.1186/s40035-020-
00221-2.
102. Vafaei-Nezhad S, Niknazar S, Norouzian M, Abdollahifar
MA, Aliaghaei A, Abbaszadeh HA. Therapeutics effects of
[Pyr1] apelin-13 on rat contusion model of spinal cord injury:
an experimental study. J Chem Neuroanat. 2021;113:101924.
doi: 10.1016/j.jchemneu.2021.101924.
103. Sarhan NR, Taalab YM. Oxidative stress/PERK/apoptotic
pathways interaction contribute to tramadol neurotoxicity in
rat cerebral and cerebellar cortex and thyme enhances the
antioxidant defense system: histological, immunohistochemical
and ultrastructural study. Int J Sci Rep. 2018;4(6):124-41. doi:
10.18203/issn.2454-2156.IntJSciRep20182083.
104. Huang Z, Zhou T, Sun X, Zheng Y, Cheng B, Li M, et al.
Necroptosis in microglia contributes to neuroinflammation
and retinal degeneration through TLR4 activation. Cell Death
Differ. 2018;25(1):180-9. doi: 10.1038/cdd.2017.141.
105. Ghafari S, Golalipour MJ. Prenatal morphine exposure
reduces pyramidal neurons in CA1, CA2 and CA3 subfields of
mice hippocampus. Iran J Basic Med Sci. 2014;17(3):155-61.
doi: 10.22038/ijbms.2014.2400.