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Home / Equine Research Bank / Front Vet Sci / Analgesic efficacy of tapentadol in chronic joint disorders ...
Frontiers in veterinary science2024; 11; 1505398; doi: 10.3389/fvets.2024.1505398

Analgesic efficacy of tapentadol in chronic joint disorders in horses: plasma serotonin concentration and adrenocortical response as biomarkers of pain-induced stress.

Abstract: The study aimed to evaluate the analgesic efficacy of tapentadol in horses, by determining plasma serotonin concentration and adrenocortical response, as biomarkers of pain stress in chronic joint disorders. Thirty-six horses (20 females and 16 males) were divided into three groups of 12 subjects each: group A, osteoarthritis (OA), grade 3-4 lameness; group B, OA, grade 5 lameness; and group C, no OA, no lameness, were enrolled. The orthopedic examination included flexion tests, and radiological and ultrasound examinations. The degree of lameness has been estimated from 0 to 5 according to the American Association of Equine Practitioners (AAEPs). Heart and respiratory rates (HR and RR) and blood pressure were recorded. Serotonin concentration and circulating cortisol levels were determined at baseline and the end of every week for 4 weeks. Biochemical parameters were recorded at baseline and the end of treatment with tapentadol. Subjects with OA were treated with tapentadol 0.5 mg kg-1. The response to painful stimulus on flexion tests was evaluated using the modified numeric pain rating scale (modified NRS 0-7) from baseline and the cumulative pain score (CPS 0-4) after the first week of treatment with tapentadol. The lameness decreased throughout the timeline in both groups (score from 3-4 to 1 in group A and score from 5 to 1 in group B) (p < 0.05). The NRS score decreased throughout the timeline (p < 0.05), from mild pain to no pain in group A (score 1-3 to 0) and from moderate pain to no pain in group B (score from 4 to 0). Physiological variables remained within the physiological range throughout the timeline. Cumulative pain scores ranged from 0.5 to 4 in group A and 1.5 to 7 in group B (p = 0.008). Serotonin concentrations remained unchanged throughout the timeline in all groups (p = 1.000) but in the OA groups, the concentrations were lower than control (p < 0.001). Circulating cortisol levels were reduced compared to baseline in subjects treated with tapentadol (p < 0.001). Tapentadol is effective in OA pain management in horses. Serotonin and cortisol may be utilized as biomarkers in the pain stress response. Serotonin can also determine the state of wellbeing of patients.
Copyright © 2024 Costa, Tabbì, Bruschetta, Spadola, Leonardi, Bruno, Iannelli, Licata, Macrì, Passino, Macrì and Interlandi.
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Publication Date: 2024-12-17 PubMed ID: 39742317PubMed Central: PMC11686550DOI: 10.3389/fvets.2024.1505398Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article studies the impact of a drug called tapentadol on horses with chronic joint disorders, by measuring its analgesic (pain-relieving) effectiveness through levels of plasma serotonin and adrenocortical response.

Study Design and Methodology

  • The study involved 36 horses, including both males and females. These horses were divided into three groups: group A had osteoarthritis and lameness of grade 3-4, group B had osteoarthritis and grade 5 lameness, and group C was the control group with no osteoarthritis or lameness.
  • All of the horses underwent an orthopedic examination which involved flexion tests as well as radiological and ultrasound examinations.
  • Lameness in the horses was graded on a scale from 0 to 5 based on guidelines from the American Association of Equine Practitioners (AAEPs).
  • Physiological parameters such as heart and respiratory rates and blood pressure were recorded, along with serotonin concentration and cortisol levels at baseline and then every week for 4 weeks.
  • Horses with osteoarthritis were treated with 0.5 mg kg of tapentadol.

Findings of the Study

  • The degree of lameness shown by the horses decreased over the study period in both group A and group B. Scores moved from 3-4 to 1 in group A and from 5 to 1 in group B, indicating significant improvement.
  • The NRS (numeric pain rating scale) scores also showed improvement, with pain going from mild to none in group A and moderate to none in group B.
  • Physiological variables such as heart rate, respiratory rate, and blood pressure remained within normal ranges throughout the study period.
  • Interestingly, serotonin concentrations remained unchanged through the timeline for all groups, but were lower in the osteoarthritis (OA) groups compared to the control group.
  • Cortisol levels, on the other hand, were reduced compared to baseline levels in the subjects treated with tapentadol.

Significance of the Research

  • The research showed that tapentadol was effective in managing pain due to osteoarthritis in horses.
  • Another important contribution of this research is the indication that serotonin and cortisol can be used as biomarkers for pain stress response.
  • This means that they could potentially be used to assess the well-being of patients and measure the effectiveness of pain management strategies.

Cite This Article

APA
Costa GL, Tabbì M, Bruschetta G, Spadola F, Leonardi F, Bruno F, Iannelli NM, Licata P, Macrì F, Passino ES, Macrì D, Interlandi C. (2024). Analgesic efficacy of tapentadol in chronic joint disorders in horses: plasma serotonin concentration and adrenocortical response as biomarkers of pain-induced stress. Front Vet Sci, 11, 1505398. https://doi.org/10.3389/fvets.2024.1505398

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 11
Pages: 1505398

Researcher Affiliations

Costa, Giovanna Lucrezia
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Tabbì, Marco
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Bruschetta, Giuseppe
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Spadola, Filippo
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Leonardi, Fabio
  • Department of Veterinary Sciences, University of Parma, Parma, Italy.
Bruno, Fabio
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Iannelli, Nicola Maria
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Licata, Patrizia
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Macrì, Francesco
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.
Passino, Eraldo Sanna
  • Department of Veterinary Medicine, University of Sassari, Sassari, Italy.
Macrì, Daniele
  • Zooprophylactic Institute, Palermo, Italy.
Interlandi, Claudia
  • Department of Veterinary Sciences, University of Messina, Messina, Italy.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 65 references
  1. Reis IL, Lopes B, Sousa P, Sousa AC, Caseiro AR, Mendonça CM. Equine musculoskeletal pathologies: clinical approaches and therapeutical perspectives—a review. Vet Sci (2024) 11:190.
    doi: 10.3390/vetsci11050190pmc: PMC11126110pubmed: 38787162google scholar: lookup
  2. Smith RK, CW MI. “One health” in tendinopathy research: current concepts. J Orthop Res (2021) 39:1596–602.
    doi: 10.1002/jor.25035pubmed: 33713481google scholar: lookup
  3. Rogers CW, Bolwell CF, Gee EK, Rosanowski SM. Equine musculoskeletal development and performance: impact of the production system and early training. Anim Prod Sci (2020) 60:2069–79.
    doi: 10.1071/AN17685google scholar: lookup
  4. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. Bone Joint Res (2012) 1:297–309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  5. Michalska J, Nowicka B, Wessely-Szponder J. Relationship between neutrophil activity, oxidative stress, acute phase response, and lameness grade in naturally occurring acute and chronic joint disorders in horses. J Equine Vet (2020) 88:102972.
    doi: 10.1016/j.jevs.2020.102972pubmed: 32303320google scholar: lookup
  6. Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse - a review. Vet J (2006) 171:51–69.
    doi: 10.1016/j.tvjl.2004.07.008pubmed: 16427582google scholar: lookup
  7. Costa GL, Leonardi F, Licata P, Tabbì M, Iannelli N, Iannelli D. Effect of surgery on oxidative stress and endogenous tocopherol concentrations in juvenile female dogs. Acta Vet Scand (2024) 66:30.
    doi: 10.1186/s13028-024-00753-xpmc: PMC11241787pubmed: 38992641google scholar: lookup
  8. Hernández-Avalos I, Flores-Gasca E, Mota-Rojas D, Casas-Alvarado A, Miranda-Cortés AE, Domínguez-Oliva A. Neurobiology of anesthetic-surgical stress and induced behavioral changes in dogs and cats: a review. Vet World (2021) 14:393–404.
    doi: 10.14202/vetworld.2021.393-404pmc: PMC7994130pubmed: 33776304google scholar: lookup
  9. Nazifi S, Shojaee Tabrizi A, Mohammadi S, Erjaee H, Mirzaie AJCCP. The effect of tramadol and meloxicam, alone and in combination on oxidative stress status in dogs. Compar Clin Pathol (2019) 28:1055–60.
    doi: 10.1007/s00580-019-02927-wgoogle scholar: lookup
  10. Vadivelu N, Mitra S, Schermer E, Kodumudi V, Kaye AD, Urman RD. Preventive analgesia for postoperative pain control: a broader concept. Local Reg Anesthesia (2014) 7:17–22.
    doi: 10.2147/LRA.S62160pmc: PMC4012350pubmed: 24872720google scholar: lookup
  11. Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT. Non-steroidal anti-inflammatory drugs in equine orthopaedics. Equine Vet J (2022) 54:636–48.
    doi: 10.1111/evj.13561pmc: PMC9304133pubmed: 35076950google scholar: lookup
  12. Leonardi F, Costa G, Dubau M, Sabbioni A, Simonazzi B, Angelone M. Effects of intravenous romifidine, detomidine, detomidine combined with butorphanol, and xylazine on tear production in horses. Equine Vet Educ (2018) 32:53–7.
    doi: 10.1111/eve.13040pubmed: 0google scholar: lookup
  13. Fisher K, Coderre TJ, Hagen NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manag (2000) 20:358–73.
    doi: 10.1016/S0885-3924(00)00213-Xpubmed: 11068158google scholar: lookup
  14. Fugazzola MC, Wever KE, van de Lest C, de Grauw J, Salvatori D. Reporting of anaesthesia and pain management in preclinical large animal models of articular cartilage repair - a long way to go. Osteoarthritis Cartilage Open (2022) 4:100261.
    doi: 10.1016/j.ocarto.2022.100261pmc: PMC9718186pubmed: 36475287google scholar: lookup
  15. Giorgi M, Meizler A, Mills PC. Pharmacokinetics of the novel atypical opioid tapentadol following oral and intravenous administration in dogs. Vet J (2012) 194:309–13.
    doi: 10.1016/j.tvjl.2012.05.019pubmed: 22771148google scholar: lookup
  16. Interlandi C, Tabbi M, Di Pietro S, D'Angelo F, Costa GL, Arfuso F. Improved quality of life and pain relief in mature horses with osteoarthritis after oral transmucosal cannabidiol oil administration as part of an analgesic regimen. Front Vet Sci (2024) 11:1341396.
    doi: 10.3389/fvets.2024.1341396pmc: PMC10876772pubmed: 38379920google scholar: lookup
  17. Costa GL, Cristarella S, Quartuccio M, Interlandi C. Anti-nociceptive and sedative effects of romifidine, tramadol and their combination administered intravenously slowly in ponies. Vet Anaesth Analg (2015) 42:220–5.
    doi: 10.1111/vaa.12210pubmed: 25039663google scholar: lookup
  18. Domínguez-Oliva A, Casas-Alvarado A, Miranda-Cortés AE, Hernández-Avalos I. Clinical pharmacology of tramadol and tapentadol, and their therapeutic efficacy in different models of acute and chronic pain in dogs and cats. J Adv Vet Anim Res (2021) 8:404–22.
    doi: 10.5455/javar.2021.h529pmc: PMC8520146pubmed: 34722739google scholar: lookup
  19. Monteiro BP, Lascelles BDX, Murrell J, Robertson S, Steagall PVM, Wright B. 2022 WSAVA guidelines for the recognition, assessment and treatment of pain. J Small Anim Pract (2023) 64:177–254.
  20. Flood J, Stewart AJ. Non-steroidal anti-inflammatory drugs and associated toxicities in horses. Animals (Basel) (2022) 12:2939.
    doi: 10.3390/ani12212939pmc: PMC9655344pubmed: 36359062google scholar: lookup
  21. Mercer MA, Davis JL, McKenzie HC. The clinical pharmacology and therapeutic evaluation of non-steroidal anti-inflammatory drugs in adult horses. Animals (Basel) (2023) 13:1597.
    doi: 10.3390/ani13101597pmc: PMC10215112pubmed: 37238029google scholar: lookup
  22. Interlandi C, Leonardi F, Spadola F, Costa GL. Evaluation of the paw withdrawal latency for the comparison between tramadol and butorphanol administered locally, in the plantar surface of rat, preliminary study. PLoS One (2021) 16:e0254497.
    doi: 10.1371/journal.pone.0254497pmc: PMC8312927pubmed: 34310642google scholar: lookup
  23. Interlandi C, Calapai G, Nastasi B, Mannucci C, Morici M, Costa GL. Effects of atipamezole on the analgesic activity of butorphanol in rats. J Exotic Pet Med (2017) 26:290–3.
    doi: 10.1053/j.jepm.2017.07.001google scholar: lookup
  24. Simon BT, Steagall PV. The present and future of opioid analgesics in small animal practice. J Vet Pharmacol Ther (2017) 40:315–26.
    doi: 10.1111/jvp.12377pubmed: 27900781google scholar: lookup
  25. Costa GL, Spadola F, Di Pietro S, Nava V, Licata P, Giudice E. Tramadol vs. lidocaine administered Intraperitoneally and in incisional lines for the intraoperative and postoperative pain management of romifidine-telazol-anesthetized swine undergoing umbilical hernia repair. Animals (Basel) (2023) 13:2905.
    doi: 10.3390/ani13182905pmc: PMC10525986pubmed: 37760305google scholar: lookup
  26. Costa G, Musicò M, Spadola F, Cortigiani S, Leonardi F, Cucinotta G. Effects of tramadol slow injection vs fast bolus in the therapeutic balance of the foot in bovine. Large Anim Rev (2018) 24:219–21.
  27. Giorgi M. Tramadol vs tapentadol: anew horizon in pain treatment?. Am J Anim Vet Sci (2012) 7:7–11.
    doi: 10.3844/ajavsp.2012.7.11google scholar: lookup
  28. Polati E, Canonico PL, Schweiger V, Collino M. Tapentadol: an overview of the safety profile. J Pain Res (2019) 12:1569–76.
    doi: 10.2147/JPR.S190154pmc: PMC6529613pubmed: 31190968google scholar: lookup
  29. Bradbrook CA, Clark L. State of the art analgesia- recent developments in pharmacological approaches to acute pain management in dogs and cats. Part 1. Vet J (2018) 238:76–82.
    doi: 10.1016/j.tvjl.2018.06.003pubmed: 29907456google scholar: lookup
  30. Kress HG. Tapentadol and its two mechanisms of action: is there a new pharmacological class of centrally-acting analgesics on the horizon?. Eur J Pain (London, England) (2010) 14:781–3.
    doi: 10.1016/j.ejpain.2010.06.017pubmed: 20659810google scholar: lookup
  31. Doodnaught GM, Evangelista MC, Steagall PVM. Thermal antinociception following oral administration of tapentadol in conscious cats. Vet Anaesth Analg (2017) 44:364–9.
    doi: 10.1016/j.vaa.2016.05.001pubmed: 28242230google scholar: lookup
  32. Faria J, Barbosa J, Moreira R, Queirós O, Carvalho F, Dinis-Oliveira RJ. Comparative pharmacology and toxicology of tramadol and tapentadol. Eur J Pain (London, England) (2018) 22:827–44.
    doi: 10.1002/ejp.1196pubmed: 29369473google scholar: lookup
  33. Kieves NR, Howard J, Lerche P, Lakritz J, Aarnes TK. Effectiveness of tapentadol hydrochloride for treatment of orthopedic pain in dogs: a pilot study. Can Vet J (2020) 61:289–93.
    pmc: PMC7020636pubmed: 32165753
  34. Howard J, Aarnes TK, Dyce J, Lerche P, Wulf LW, Coetzee JF. Pharmacokinetics and pharmacodynamics after oral administration of tapentadol hydrochloride in dogs. Am J Vet Res (2018) 79:367–75.
    doi: 10.2460/ajvr.79.4.367pubmed: 29583048google scholar: lookup
  35. Giorgi M, Mills PC, Tayari H, Rota S, Breghi G, Briganti A. Plasma concentrations of tapentadol and clinical evaluations of a combination of tapentadol plus sevoflurane for surgical anaesthesia and analgesia in rabbits (Oryctolagus cuniculus) undergoing orchiectomy. Isr J Vet (2013) 68:141–8.
  36. Tzschentke TM, Christoph T, Kögel BY. The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MOR–NRI) concept in analgesia: the case of tapentadol. CNS Drugs (2014) 28:319–29.
    doi: 10.1007/s40263-014-0151-9pubmed: 24578192google scholar: lookup
  37. Tschentke T, De Vry J, Terlinden R, Hennies H-H, Lange C, Strassburger W. Tapentadol hydrochloride. Drugs Future (2006) 31:1053.
    doi: 10.1358/dof.2006.031.12.1047744pubmed: 0google scholar: lookup
  38. Interlandi C, Nastasi B, Morici M, Calabrò P, Costa GL. Effects of the combination romifidine/tramadol drug administration on several physiological and behavioral variables in calves. Large Anim Rev (2017) 23:51–4.
  39. Costa G, Spadola F, Lentini M, Lubian E, Leonardi F. Comparison of analgesia and ataxia degree obtained between three dosages of tramadol in cattle. Large Anim Rev (2021) 27:65–8.
  40. Roulet L, Rollason V, Desmeules J, Piguet V. Tapentadol versus tramadol: a narrative and comparative review of their pharmacological, efficacy and safety profiles in adult patients. Drugs (2021) 81:1257–72.
    doi: 10.1007/s40265-021-01515-zpmc: PMC8318929pubmed: 34196947google scholar: lookup
  41. Raghupathi RK, McGonigle PJN. Differential effects of three acute stressors on the serotonin 5-HT1A receptor system in rat brain. Neuroendocrinology (1997) 65:246–58.
    pubmed: 9142996
  42. Herr N, Bode C, Duerschmied D. The effects of serotonin in immune cells. Front Cardiovasc Med (2017) 4:48.
    doi: 10.3389/fcvm.2017.00048pmc: PMC5517399pubmed: 28775986google scholar: lookup
  43. Moteshakereh SM, Nikoohemmat M, Farmani D, Khosrowabadi E, Salehi S, Haghparast A. The stress-induced antinociceptive responses to the persistent inflammatory pain involve the orexin receptors in the nucleus accumbens. Neuropeptides (2023) 98:102323.
    doi: 10.1016/j.npep.2023.102323pubmed: 36736068google scholar: lookup
  44. Tsigos C, Kyrou I, Kassi E, Chrousos GP. Stress: endocrine physiology and pathophysiology. Endotext [Internet] (2020).
  45. Butler RK, Finn DP. Stress-induced analgesia. Prog Neurobiol (2009) 88:184–202.
    doi: 10.1016/j.pneurobio.2009.04.003pubmed: 19393288google scholar: lookup
  46. Rankins EM, Manso Filho HC, Malinowski K, McKeever KH. Muscular tension as an indicator of acute stress in horses. Physiol Rep (2022) 10:e15220.
    doi: 10.14814/phy2.15220pmc: PMC8935158pubmed: 35307975google scholar: lookup
  47. Thau L, Gandhi J, Sharma S. Physiology, Cortisol. StatPearls [Internet] [Updated 2023 Aug 28]. (2024).
    pubmed: 30855827
  48. Ambrojo KS, Corzano MM, Poggi JCG. Action mechanisms and pathophysiological characteristics of cortisol in horses. London, UK: IntechOpen; (2018). 185 p..
  49. Medica P, Cravana C, Bruschetta G, Ferlazzo A, Fazio E. Breeding season and transport interactions on the pituitary-adrenocortical and biochemical responses of horses. J Vet Behav (2018) 23:91–6.
    doi: 10.1016/j.jveb.2017.11.003google scholar: lookup
  50. Costa GL, Leonardi F, Interlandi C, Licata P, Lizarraga I, Macrì F. Tramadol administered intravenously either as a bolus or a slow injection in pain management of romifidine-sedated calves undergoing umbilical hernia repair. Animals (2023) 13:1145.
    doi: 10.3390/ani13071145pmc: PMC10093555pubmed: 37048401google scholar: lookup
  51. Medica P, Cravana C, Bruschetta G, Ferlazzo A, Fazio E. Physiological and behavioral patterns of normal-term thoroughbred foals. J Vet Behav (2018) 26:38–42.
    doi: 10.1016/j.jveb.2018.04.002google scholar: lookup
  52. Bruschetta G, Bionda A, Giunta RP, Costa GL, Fazio E, Licata P. Can productive aptitude and age affect circulating serotonin, Total thyroid hormones, and cortisol patterns in cows?. Vet Sci (2024) 11:471.
    doi: 10.3390/vetsci11100471pmc: PMC11512262pubmed: 39453063google scholar: lookup
  53. Bruschetta G, Zanghì G, Giunta RP, Ferlazzo AM, Satué K, D’Ascola A. Short road transport and slaughter stress affects the expression profile of serotonin receptors, adrenocortical, and hematochemical responses in horses. Vet Sci (2024) 11:113.
    doi: 10.3390/vetsci11030113pmc: PMC10974429pubmed: 38535847google scholar: lookup
  54. Bruschetta G, Leonardi F, Licata P, Iannelli NM, Fernàndez-Parra R, Bruno F. Oxidative stress in relation to serotonin under general anaesthesia in dogs undergoing ovariectomy. Vet Q (2024) 44:1–8.
    doi: 10.1080/01652176.2024.2379319pmc: PMC11262201pubmed: 39028214google scholar: lookup
  55. Linthorst A, Reul J. The impact of stress on serotonergic neurotransmission. Handb. Behav. Neurosci. (2010) 21:475–491.
    doi: 10.1016/S1569-7339(10)70097-7google scholar: lookup
  56. Wu H, Denna TH, Storkersen JN, Gerriets VA. Beyond a neurotransmitter: the role of serotonin in inflammation and immunity. Pharmacol Res (2019) 140:100–14.
    doi: 10.1016/j.phrs.2018.06.015pubmed: 29953943google scholar: lookup
  57. Santos J, Alarcão J, Fareleira F, Vaz-Carneiro A, Costa J. Tapentadol for chronic musculoskeletal pain in adults. Cochrane Database Syst Rev (2015) 2015:Cd009923.
    doi: 10.1002/14651858.CD009923.pub2pmc: PMC7205027pubmed: 26017279google scholar: lookup
  58. de Las C-EM, Corbí AL. Serotonin modulation of macrophage polarization: inflammation and beyond. Adv Exp Med Biol (2014) 824:89–115.
    doi: 10.1007/978-3-319-07320-0_9pubmed: 25038996google scholar: lookup
  59. Nieto C, Rayo I, de Las C-EM, Izquierdo E, Alonso B, Béchade C. Serotonin (5-HT) shapes the macrophage gene profile through the 5-HT(2B)-dependent activation of the aryl hydrocarbon receptor. J Immunol (2020) 204:2808–17.
    doi: 10.4049/jimmunol.1901531pubmed: 32253244google scholar: lookup
  60. Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E. Serotonin-evoked cytosolic ca(2+) release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses. Vet Anim Sci (2019) 8:100078.
    doi: 10.1016/j.vas.2019.100078pmc: PMC7386637pubmed: 32734095google scholar: lookup
  61. Hunter JN, Wood EK, Roberg BL, Neville L, Schwandt ML, Fairbanks LA. Mismatches in resident and stranger serotonin transporter genotypes lead to escalated aggression, and the target for aggression is mediated by sex differences in male and female rhesus monkeys (Macaca mulatta). Horm Behav (2022) 140:105104.
    doi: 10.1016/j.yhbeh.2021.105104pmc: PMC9380749pubmed: 35180497google scholar: lookup
  62. Gotlib IH, Joormann J, Minor KL, Hallmayer J. HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biol Psychiatry (2008) 63:847–51.
    doi: 10.1016/j.biopsych.2007.10.008pmc: PMC2373542pubmed: 18005940google scholar: lookup
  63. Ayala I, Martos NF, Silvan G, Gutierrez-Panizo C, Clavel JG, Illera JC. Cortisol, adrenocorticotropic hormone, serotonin, adrenaline and noradrenaline serum concentrations in relation to disease and stress in the horse. Res Vet Sci (2012) 93:103–7.
    doi: 10.1016/j.rvsc.2011.05.013pubmed: 21641009google scholar: lookup
  64. Bruschetta G, Di Pietro P, Fazio E, Ferlazzo AM. Plasma serotonin, tryptophan, hematological, and functional responses to horse trekking. J Vet Behav (2014) 9:248–53.
    doi: 10.1016/j.jveb.2014.06.001google scholar: lookup
  65. Chaouloff F. Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev (1993) 18:1–32.
    doi: 10.1016/0165-0173(93)90005-Kpubmed: 8467346google scholar: lookup
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