Tramadol effects on the nucleus accumbens – insights from in vitro and in vivo studies

Authors

  • Sara Pinho Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal https://orcid.org/0009-0007-1143-8138
  • Ricardo Jorge Dinis-Oliveira Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal; Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; FOREN – Forensic Science Experts, 1400-136 Lisboa, Portugal
  • Juliana Faria Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
  • Joana Barbosa Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal

DOI:

https://doi.org/10.48797/sl.2024.252

Keywords:

Poster

Abstract

Background: Tramadol is mainly used for the treatment of moderate to severe pain. It synergistically combines two distinct mechanisms of action, being a selective agonist for mu-opioid receptors (MOR) and inhibiting serotonin and noradrenaline reuptake, which improves its analgesic and safety profile [1]. However, it is not devoid of neurobehavioral toxicity potential [2], whose molecular alterations are not fully clarified. Due to its primary role in reward, motivation and drug self-administration behaviors, the nucleus accumbens (NAC) is anticipated to participate in the mechanisms of tramadol addiction, dependence and toxicity. Objective: The aim of this review is to summarize the main neurotoxicity biomarkers and effects of tramadol exposure on the NAC. Methods: A bibliographic research of neurotoxicity biomarkers and findings concerning the NAC, upon exposure to tramadol, was performed on the National Library of Medicine (PubMed), with no temporal restrictions and considering in vitro and in vivo studies. Results: In vivo studies showed increased levels of MOR, p-CREB and deltaFosB in the NAC after acute and chronic exposure to tramadol (5 and 10 mg/kg) [3]. Even if apoptosis and inflammation are major NAC findings in in vivo studies, autophagy was also upregulated in in vitro studies with PC12 cells exposed to 50 mM tramadol [4]. In addition, it has been found that tramadol enhances dopamine levels in the NAC shell and that NAC cannabinoid receptor 1 (CB1R) is involved in tramadol reinforcing effect and reinstatement [5]. Conclusions: In conclusion, although tramadol controls pain more effectively and with fewer adverse events than classical opioids, its neurotoxic potential is of particular concern. The nucleus accumbens has a relevant contribution to such neurobehavioral toxicity, as shown by multiple alterations in important cell death, inflammation and related signaling pathways. A personalized and cautious tramadol prescription is thus mandatory.

References

1. Faron-Górecka, A.; Kuśmider, M.; Inan, S. Y.; Siwanowicz, J.; Piwowarczyk, T; Dziedzicka-Wasylewska, M. Long-term exposure of rats to tramadol alters brain dopamine and alpha 1-adrenoceptor function that may be related to antidepressant potency. Eur J Pharmacol (2004), 501(1–3), 103–110.

2. Barbosa, J.; Leal, S.; Pereira, F.C.; Dinis-Oliveira, R.J.; Faria, J. Tramadol and Tapentadol Induce Conditioned Place Preference with a Differential Impact on Rewarding Memory and Incubation of Craving. Pharmaceuticals (2023), 16, 86.

3. Sadat-Shirazi, M.-S.; Babhadi-Ashar, N.; Khalifeh, S.; Mahboubi, S.; Ahmadian-Moghaddam, H.; Zarrindast, M.-R. Tramadol induces changes in Δ-FosB, µ-opioid receptor, and p-CREB level in the nucleus accumbens and prefrontal cortex of male Wistar rat. Am J Drug Alcohol Abuse (2019), 45(1), 84–89.

4. Soltani, R.; Boroujeni, M. E.; Aghajanpour, F.; Khatmi, A.; Ezi, S.; Mirbehbahani, S. H.; Abdollahifar , M.-A.; Akhlaghpasan, M.; Aliaghaei, A.; Heidari, M.-H. 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.

5. Sadeghi-Adl, M.; Sadat-Shirazi, M.-S; Shahini, F.; Akbarabadi, A.; Khalifeh, S.; Borzabadi, S.; Nasehi, M.; Zarrindast, M.-R. The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement. Life Sci (2020), 260, 118430.

Downloads

Published

2024-05-01

How to Cite

Pinho , S., Dinis-Oliveira , R. J., Faria , J., & Barbosa, J. (2024). Tramadol effects on the nucleus accumbens – insights from in vitro and in vivo studies. Scientific Letters, 1(Sup 1). https://doi.org/10.48797/sl.2024.252

Issue

Section

Posters

Most read articles by the same author(s)

Similar Articles

<< < 1 2 3 4 5 6 7 8 9 10 > >> 

You may also start an advanced similarity search for this article.