Effects of alcohol and tramadol co-treatment on cognitive functions and neuro-inflammatory responses in the medial prefrontal cortex of juvenile male rats

Year 2019, Volume: 13 Issue: 1, 1 - 12, 29.04.2019

Damilare Adedayo Adekomi , Adebiyi Aderinola Adegoke Olayinka Olaolu Olaniyan Adepeju Ester Ogunrinde Olayemi Kafilat Ijomone

Abstract

Objectives: Misuse and abuse of drugs are on the increase amongst juvenile individuals across the world. This study was
carried out to evaluate the cognitive and subcellular neuropathologic events in the medial prefrontal cortex (mPFC) of juvenile male rats following exposure to alcohol and tramadol hydrochloride.

Methods: The rats were assigned into four groups; vehicle group, alcohol group, tramadol group, and the alcohol+tramadol
combined group. Twenty-four hours after the administration of the last dose, 5 rats from each group were sacrificed. The mPFCs
were excised and were stained with either cresyl violet or glia fibrillary acidic protein immunoreactivity. The remaining rats in each
of the groups were subjected to cognitive behavioural tests.

Results: The administration of alcohol, tramadol and the co-administration of alcohol+tramadol triggers astrogliosis, glial scars
and inflammatory responses relative to the vehicle-treated with well-preserved profile. The distribution of Nissl substances suggested that the neurons are either undergoing neurodegeneration or neuronal metabolism impairment. The behavioural tests
showed that the administration of the respective substances impaired cognition in the treated rats compared to the vehicle-treated rats.

Conclusion: This study concluded that alcohol, tramadol, and alcohol+tramadol misuse can impair the functional integrity
of the medial prefrontal cortex. 

Keywords

brain; cognition; drug misuse; learning; memory; neural degeneration

References

• 1. Pothiawala S, Ponampalam R. Tramadol overdose: a case report. Proceedings of Singapore Healthcare 2011;20:219–23. 2. Abdel-Salam OME, Youness ER, Khadrawy YA, Sleem AA. Acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis, tramadol or both. Asian Pacific Journal of Tropical Medicine 2016;9:1089–94. 3. Duvall A. Tramadol. Therapeutic Review 2017;26:74–7. 4. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004;43:879–923. 5. Ryan NM, Isbister GK. Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely. Clin Toxicol (Phila) 2015;53:545–50. 6. Mobasher MA, Sajedianfard J, Jamshidzadeh A, Naghdi N, Namvaran MM. The effects of tramadol on norepinephrine and MHPG releasing in locus coeruleus in formalin test in rats: a brain stereotaxic study. Iran J Basic Med Sci 2014;17:419–25. 7. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs 2000;60:139–76. 8. Babul N, Noveck R, Chipman H, Roth SH, Gana T, Albert K. Efficacy and safety of extended- release once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee. J Pain Symptom Manage 2004;28:59–71. 9. Khodeary MF, Sharaf El-Din AAI, El Kholy SMS. A histopathological and immunohistochemical study of adult rats’ brain after longterm exposure to amadol (tramadol hydrochloride). Mansoura Journal of Forensic Medicine and Clinical Toxicology 2010;18:1–24. 10. Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Mico JA. Antidepressant-like effect of tramadol and its enantiomers in reserpinized mice: comparative study with desipramine, fluvoxamine, venlafaxine and opiates. J Psychopharmacol 2004;18:404–11.11. Threlkeld M, Parran TV Adelman CA, Grey SF, Yu J. Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study. Am. J Addict 2006;15:186–91. 12. Salem EA, Wilson SK, Bissada NK. Tramadol HCL has promise in on-demand use to treat premature ejaculation. J Sex Med 2008;5: 188–93. 13. Nicholas R, Lee N, Roche A. Pharmaceutical drug misuse in Australia: complex problems, balanced responses. Adelaide: National Centre for Education and Training on Addiction (NCETA), Flinders University; 2011. 14. Clarkson JE, Lacy JM, Fligner CL, Thiersch N, Howard J, Harruff RC, Logan BK. Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance. J Forensic Sci 2004;49:1101–5. 15. Saunders KW, Von Korff M, Campbell CI, Banta-Green CJ, Sullivan MD, Merrill JO, Weisner C. Concurrent use of alcohol and sedatives among persons prescribed chronic opioid therapy: prevalence and risk factors. J Pain 2012;13:266–75. 16. Shadnia S, Soltaninejad K, Heydari K, Sasanian G, Abdollahi M. Tramadol intoxication: a review of 114 cases. Hum Exp Toxicol 2008;27:201–5. 17. Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, Pickering RP, Ruan WJ, Smith SM, Huang B, Hasin DS. Epidemiology of DSM-5 alcohol use disorder: results from the national epidemiologic survey on alcohol and related conditions. III. JAMA Psychiatry 2015;72:757–66. 18. Enoch MA, Goldman D. The genetics of alcoholism and alcohol abuse. Curr Psychiatry Rep 2001;3:144–51. 19. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Publishing; 2013. 20. Dumbili E. Changing patterns of alcohol consumption in Nigeria: an exploration of responsible factors and consequences. Medical Sociology Online 2013;7:20–33. 21. Guerri C, Bazinet A, Riley EP. Foetal alcohol spectrum disorders and alterations in brain and behaviour, alcohol and alcoholism. Alcohol Alcohol 2009;44:108–14. 22. Wilhelm CJ, Guizzetti M. Fetal alcohol spectrum disorders: an overview from the glia perspective. Front Integr Neurosci 2015;9:65. 23. Adekomi DA, Adewole OS, Dare BJ, Olaniyan OO, Ojebisi RM, Ajao MS. Alcohol-pentazocine combination: implication on the cytoarchitectural profile of the medial prefrontal cortex and cerebellum of juvenile male rats. Anatomy Journal of Africa 2017;6:1080– 91. 24. Guerri C, Pascual M. Mechanisms involved in the neurotoxic, cognitive, and neurobehavioral effects of alcohol consumption during adolescence. Alcohol 2010;44:15–26. 25. Alfonso-Loeches S, Guerri C. Molecular and behavioural aspects of the actions of alcohol on the adult and developing brain. Crit Rev Clin Lab Sci 2011;48:19–47. 26. Fuster JM. The prefrontal cortex - an update: time is of the essence. Neuron 2001;30:319–33. 27. Kolb B, Mychasiuk R, Muhammad A, Li Y, Frost DO, Gibb R. Experience and the developing prefrontal cortex. Proc Natl Acad Sci U S A 2012;109:17186–93. 28. Shekarchizadeh H, Khami MR, Mohebbi SZ, Ekhtiari H, Virtanen JI. Oral health of drug abusers: a review of health effects and care. Iran J Public Health 2013;42:929–40. 29. Guide for the Care and Use of Laboratory Animals. National Research Council (US) Committee for the update of the guide for the care and use of laboratory animals. 8th edition. Washington, DC: National Academies Press (US); 2011. 30. Piermartiri TC, Figueiredo CP, Rial D, Duarte FS, Bezerra SC, Mancini G, de Bem AF, Prediger RD, Tasca CI. Atrovastatin prevents hippocampal cell death, neuroinflammation and oxidative stress following amyloid-β1-40 administration in mice: Evidence for dissociation between cognitive deficits and neuronal damage. Exp Neurol 2010;226:274–84. 31. Yan JJ, Cho JY, Kim HS, Kim KL, Jung JS, Huh SO, Suh HW, Kim YH, Song DK. Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br J Pharmacol 2001;133:89–96. 32. Adekomi DA, Adegoke AA, Adekilkeun TA, Olaniyan OO, Alabi MO, Ijomone KO. Morphine-alcohol treatment impairs cognitive functions and increases neuro-inflammatory responses in the medial prefrontal cortex of juvenile male rats. Anat Cell Biol 2018; 51:41–51. 33. Marco EM, Peñasco S, Hernández MD, Gil A, Borcel E, Moya M, et al. Long-term effects of intermittent adolescent alcohol exposure in male and female rats. Front Behav Neurosci 2017;11:233. 34. Hamburg H, Trossbach SV, Bader V, Chwiesko C, Kipar A, Sauvage M, Crum WR, Vernon AC, Bidmon HJ, Korth C. Simultaneous effects on parvalbumin-positive interneurons and dopaminergic system development in a transgenic rat model for sporadic schizophrenia. Sci Rep 2016;6:34946. 35. Ooigawa H, Nawashiro H, Fukui S, Otani N, Osumi A, Toyooka T, Shima K. The fate of Nissl-stained dark neurons following traumatic brain injury in rats: difference between neocortex and hippocampus regarding survival rats. Acta Neuropathol 2006;112:471–81. 36. Paxinos G, Franklin K. The mouse brain in stereotaxic coordinates. 4th ed. San Diego (CA): Elsevier Academic Press; 2013. 37. Yan T, Huan X, Wei J, Yun-Cheng N, Wei-feng Q, Peng-cheng W. Effect of tramadol with different doses on the learning and memory of mice. Journal of Jinggangshan University (Natural Science) 2011;3:28. 38. Jauhar S, Marshall EJ, Smith ID. Alcohol and cognitive impairment. Advences in Psychiatric Treatment 2014;20:304–13. 39. Hosseini-Sharifabad A, Rabbani M, Sharifzadeh M, Bagheri N. Acute and chronic tramadol administration impair spatial memory in rat. Res Pharm Sci 2016;11:49–57. 40. Ghoneim FM, Khalaf HA, Elsamanoudy AZ, Helaly AN. Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study. Int J Clin Exp Pathol 2014;7:7323–41. 41. El-Bermawy MI, Salem MF. Histological changes of the albino rat cerebellar cortex under the effect of different doses of tramadol administration. The Egyptian Journal of Histology 2015;38:143– 55. 42. Tao Q, Stone DJ, Borenstein MR, Codd EE, Coogan TP, Desai- Krieger D, Liao S, Raffa RB. Differential tramadol and O-desmethyl metabolite levels in brain vs. plasma of mice and rats administered tramadol hydrochloride orally. J Clin Pharm Ther 2002;27:99–106. 43. Alici HA, Ozmen I, Cesur M, Sahin F. Effect of the spinal drug tramadol on the fatty acid compositions of rabbit spinal cord and brain. Biol Pharm Bull 2003;26:1403–6.44. Kofke WA, Garman RH, Janosky J Rose ME. Opioid neurotoxicity: neuropathologic effects in rats of different fentanyl congeners and the effects of hexamethonium-induced normotension. Anesth Analg 1996a;83:141–6. 45. Kofke WA, Garman RH, Stiller RL, Rose ME, Garman R. Opioid neurotoxicity: fentanyl dose-response effects in rats. Anesth Analg 1996b;83:1298–306. 46. Miao H, Qin BY, Yang Y, Chen DY. Ultrastructural changes in rat locus coeruleus induced by chronic opioids. Acta Neuropathol 1997;94:109–15. 47. Alberts B, Bray D, Lewis J, Raff M, Robert K, Watson JD. In: Molecular biology of the cell. 3rd ed. New York: Garland: 1994. p. 655–720. 48. Bossert JM, Marchant NJ, Calu DJ, Shaham Y. The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology (Berl) 2013;229:453–76. 49. Lasseter HC, Xie X, Ramirez DR, Fuchs RA Prefrontal cortical regulation of drug seeking in animal models of drug relapse. Curr Top Behav Neurosci 2010;3:101–17. 50. Miguel-Hidalgo JJ. Lower packing density of glial fibrillary acidic protein-immunoreactive astrocytes in the prelimbic cortex of alcohol- naive and alcohol-drinking alcohol-preferring rats as compared with alcohol-non-preferring and Wistar rats. Alcohol Clin Exp Res 2005;29:766–72. 51. Collins MA, Corso TD, Neafsey EJ. Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic “binge” intoxication with ethanol: possible explanation for olfactory deficits in alcoholics. Alcohol Clin Exp Res 1996;20:284–92. 52. Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. Gliotransmitters travel in time and space. Neuron 2014; 81:728–39. 53. Sakurai-Yamashita Y, Yamashita K, Niwa M, Taniyawa K. Involvement of 5- hydroxytryptamine 4 receptor in the exacerbation of neuronal loss by psychological stress in the hippocampus of SHRSP with a transient ischemia. Brain Res 2003;973:92–8. 54. Tsukada H, Fukumoto D, Nishiyama S, Sato K, Kakiuchi T. Transient focal ischemia affects the cAMP second messenger system and coupled dopamine D1 and 5-HT1A receptors in the living monkey brain: a positron emission tomography study using microdialysis. J Cereb Blood Flow Metab 2004;24:898–906. 55. Singhal PC, Sharma P, Kapasi AA, Reddy K, Franki N, Gibbons N. Morphine enhances macrophage apoptosis. J Immunol 1998;160: 1886–93. 56. Chetan, PS, Ramakrishna BS, Reddanna P, Lakshmi PS, Mohan PM, Rajendra W. Tramadol effects on the activity levels of ATPases in mitochondrial fractions of rat brain areas during non-induction of pain. International Journal of Pharmacology 2007;3:341–6. 57. Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 2004;44:239–67. 58. Hauser KF, Stiene-Martin A, Mattson MP, Elde RP, Ryan SE, Godleske CC. mu-Opioid receptor-induced Ca2+ mobilization and astroglial development: morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca2+ dependent mechanism. Brain Res1996;720:191–203. 59. Eisch AJ, Barrot M, Schad CA, Self DW, Nestler EJ. Opiates inhibit neurogenesis in the adult rat hippocampus. Proc Natl Acad Sci U S A 2000;97:7579–84.