Emotiogenic effects of antorex, a novel OX1R antagonist, on emotional manifestations of anxiety and compulsiveness in rats

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: In recent years, research has focused on understanding the role of orexins and their receptors in regulating the emotions, motivations and brain reinforcing systems. Orexin plays a crucial role in the extrahypothalamic system of corticotropin-releasing hormone, making it a potential target for developing pharmacological agents to treat phobic spectrum disorders.

AIM: The study aims to analyze the effect of the new OX1R antagonist, antorex, on emotional manifestations of anxiety in rats.

MATERIALS AND METHODS: The experiments involved 38 Wistar male rats. Antorex, at a concentration of 1 µg/µl (or water as control), was intranasally administered in a volume of 20 µl (10 µl in each nostril). A battery of behavioral tests was employed, including the elevated plus maze, open field, marble test, intruder-resident test and anxiety-phobic state assessment.

RESULTS: In the elevated plus maze test, antorex showed moderate anxiolytic activity, as evidenced by the increase in the time spent in the light arm compared to the control group. The marble test revealed a decrease in the number of buried balloons after antorex administration, indicating a reduction in obsessive-compulsive state of anxiety. The anxiety-phobic state assessment test demonstrated a decrease in the avoidance reaction to the hand’s action. In the “open field” test, a decrease in motor activity was observed.

CONCLUSIONS: The OX1R antagonist antorex demonstrated an anxiolytic and sedative effect, reducing compulsive behavior without affecting the communicative activity. These findings support the potential use of drugs that modulate orexin regulation as a novel approach in the treatment of phobic spectrum disorders.

Full Text

Restricted Access

About the authors

Andrei A. Lebedev

Institute of Experimental Medicine

Author for correspondence.
Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204

Dr. Biol. Sci. (Pharmacology), head of the Laboratory of General Pharmacology, S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

Valeriya V. Lukashkova

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru

postgraduate student

Russian Federation, Saint Petersburg

Anna G. Pshenichnaya

Institute of Experimental Medicine

Email: pscanna@mail.ru

engineer, S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

Evgenii R. Bychkov

Institute of Experimental Medicine

Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799

Cand. Med. Sci. (Pathophysiology), head of the Laboratory, S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

Viktor A. Lebedev

Institute of Experimental Medicine

Email: vitya-lebedev-57@mail.ru
ORCID iD: 0000-0002-1525-8106
SPIN-code: 1878-8392

Cand. Sci. (Biol.), research associate, S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

Vladimir V. Rusanovsky

Saint Petersburg State Pediatric Medical University

Email: aalebedev-iem@rambler.ru

Dr. Sci. (Med), professor, Department of Pharmacology

Russian Federation, Saint Petersburg

Petr D. Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477

Dr. Med. Sci. (Pharmacology), professor and head of the Department, S.V. Anichkov Department of Neuropharmacology

Russian Federation, Saint Petersburg

References

  1. Daliev BB, Bychkov ER, Myznikov LV, et al. Anticompulsive effects of novel derivatives of coumarin in rats. Reviews on Clinical Pharmacology and Drug Therapy. 2021;19(3):339–344. (In Russ.) doi: 10.17816/RCF193339-344
  2. Lebedev AA, Pshenichnaya AG, Yakushina ND, et al. Effect of astressin, a corticoliberin antagonist, on aggression and anxiety-fobic states in male rats reared in social isolation. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(3):38–47. (In Russ.) doi: 10.17816/RCF15338-47
  3. Tissen IY, Lebedev AA, Bychkov ER, et al. Orexins and the brain reinforcing systems. Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(4):5–18. (In Russ.) doi: 10.17816/RCF1745-18
  4. Tissen IY, Yakushina ND, Lebedev AA, et al. Effect of SB-408124, an orexin A OX1R receptor antagonist, on the compulsive behavior and the level of anxiety after the vital stress in rats. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):34–42. (In Russ.) doi: 10.17816/RCF16134-42
  5. Tissen IY, Lebedev AA, Khokhlov PP, et al. Effect of orexin and its antagonist on the organization of emotional and exploratory behavior of rats in a model of psychic trauma. Reviews on Clinical Pharmacology and Drug Therapy. 2022;20(1):83–88. (In Russ.) doi: 10.17816/RCF20183-88
  6. Shabanov PD, Yakushina ND, Lebedev AA. Pharmacology of peptide mechanisms of gambling behavior in rats. Journal of addiction problems. 2020;(4):24–44. (In Russ.) doi: 10.47877/0234-0623_2020_4_24
  7. Akanmu MA, Honda K. Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats. Brain Res. 2005;1048(1–2):138–145. doi: 10.1016/j.brainres.2005.04.064
  8. Aston-Jones G, Smith RJ, Sartor H, et al. Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction. Brain Res. 2010;1314:74–90. doi: 10.1016/j.brainres.2009.09.106
  9. Arendt DH, Hassell J, Li H, et al. Anxiolytic function of the orexin 2 / hypocretin A receptor in the basolateral amygdala. Psychoneuroendocrinology. 2014;40:17–26. doi: 10.1016/j.psyneuen.2013.10.010
  10. De Lecea L. Hypocretins and the neurobiology of sleep-wake mechanisms. Prog Brain Res. 2012;198:234–248. doi: 10.1016/B978-0-444-59489-1.00003-3
  11. Gotter AL, Roecker AJ, Hargreaves R, et al. Orexin receptors as therapeutic drug targets. Progr Brain Res. 2012;198:48–56. doi: 10.1016/B978-0-444-59489-1.00010-0
  12. Harris GC, Aston-Jones G. Arousal and reward: a dichotomy in orexin function. Trends Neurosci. 2006;29(10):571–577. doi: 10.1016/j.tins.2006.08.002
  13. Herry C, Ciocchi S, Senn V, et al. Switching on and off fear by distinct neuronal circuits. Nature. 2008;454:600–606. doi: 10.1038/nature07166
  14. Johnson PL, Molosh A, Fitz SD, et al. Chapter 9 — Orexin, stress, and anxiety/panic states. Progr Brain Res. 2012;198:133–161. doi: 10.1016/B978-0-444-59489-1.00009-4
  15. Lebedev AA, Bessolova YN, Efimov NS, et al. Role of orexin peptide system in emotional overeating induced by brain reward stimulation in fed rats. Res Results Pharmacol. 2020;6(2):81–91. DOI: 10.3897/ rrpharmacology.6.52180
  16. Mieda M, Sakurai T. Overview of orexin/hypocretin system. Progr Brain Res. 2012;198:5–14. doi: 10.1016/B978-0-444-59489-1.00002-1
  17. Mikrouli E, Wörtwein G, Soylu R, et al. Increased numbers of orexin/hypocretin neurons in a genetic rat depression model. Neuropeptides. 2011;45(6):401–406. doi: 10.1016/j.npep.2011.07.010
  18. Myers KM, Davis M. Mechanisms of fear extinction. Mol Psychiatry. 2007;12:120–150. doi: 10.1038/sj.mp.4001939
  19. Ponz A, Khatami R, Poryazova R, et al. Reduced amygdala activity during aversive conditioning in human narcolepsy. Ann Neurol. 2010;67(3):394–398. doi: 10.1002/ana.21881
  20. Sears RM, Fink AE, Wigestrand MB, et al. Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus. PNAS USA. 2013;110(50):20260–20265. doi: 10.1073/pnas.1320325110
  21. Staples LG, Cornish JL. The orexin-1 receptor antagonist SB-334867 attenuates anxiety in rats exposed to cat odor but not the elevated plus maze: An investigation of Trial 1 and Trial 2 effects. Horm Behav. 2014;65(3):294–300. doi: 10.1016/j.yhbeh.2013.12.014
  22. Tissen I, Kurbanov R, Hohlov P, et al OX1R antagonist SB408124 action and exyrahypothalamic CRF in rats after psychotraumatic exposure. Georgian Med News. 2019;(290):127–131.

Copyright (c) 2023 ECO-vector LLC



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 65565 от 04.05.2016 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies