The inhibitory effects of orexin antagonists on the reinforcing properties of amphetamine during brain self-stimulation and the development of a conditioned place preference in rats
- Authors: Shabanov P.D.1,2, Azarenko S.V.1, Morozov V.I.1, Bessolova Y.N.1, Lebedev A.A.1
-
Affiliations:
- Institute of Experimental Medicine
- S.M. Kirov Military Medical Academy
- Issue: Vol 17, No 4 (2019)
- Pages: 57-64
- Section: Original study articles
- URL: https://journals.rcsi.science/RCF/article/view/21210
- DOI: https://doi.org/10.17816/RCF17457-64
- ID: 21210
Cite item
Full Text
Abstract
Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B18-28 in rats.
Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 µg, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula.
Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 μg, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (β-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 μg i.v.).
Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.
Full Text
##article.viewOnOriginalSite##About the authors
Petr D. Shabanov
Institute of Experimental Medicine; S.M. Kirov Military Medical Academy
Author for correspondence.
Email: pdshabanov@mail.ru
Dr. Med. Sci. (Pharmacology), Professor and Head, Dept. of Neuropharmacology; Head, Department of Pharmacology
Russian Federation, Saint PetersburgSergei V. Azarenko
Institute of Experimental Medicine
Email: azsergei@yandex.ru
Post-graduate Student, Dept. of Neuropharmacology
Russian Federation, Saint PetersburgVitalii I. Morozov
Institute of Experimental Medicine
Email: vitmoroz@yandex.ru
PhD (Narcology), Postdoc Student, Dept. of Neuropharmacology
Russian Federation, Saint PetersburgYulia N. Bessolova
Institute of Experimental Medicine
Email: juliannna_7@mail.ru
Post-graduate Student, Dept. of Neuropharmacology
Russian Federation, Saint PetersburgAndrei A. Lebedev
Institute of Experimental Medicine
Email: aalebedev-iem@rambler.ru
Dr. Biol. Sci. (Pharmacology), Head of the Laboratory of General Pharmacology, Dept. of Neuropharmacology
Russian Federation, Saint PetersburgReferences
- Айрапетов М.И., Сексте Э.А., Ереско С.О., и др. Уровень мРНК рецепторов орексина первого типа (OX1R) в эмоциогенных структурах мозга крыс при их хронической алкоголизации // Вопросы наркологии. – 2018. – № 8. – С. 18–25. [Airapetov MI, Sekste EA, Eresko SO, et al. Orexin receptor type 1 (OX1R) mRNA level in emotiogenic structures of the brain under chronic alcoholization. Voprosy narkologii. 2018;(8):18-25. (In Russ.)]
- Дробленков А.В., Федоров А.В., Маградзе Р.Н., и др. Взаимодействие нейронов орексинергического и дофаминергического ядер ствола мозга в механизме алкогольной зависимости, формируемой в перинатальном периоде // Вестник новых медицинских технологий. – 2018. – Т. 25. – № 3. – С. 137–141. [Doblenkov AV, Fedorov AV, Magradze RN, et al. Interaction of orexinergic and dopaminergic brain stem nuclei neurons in the mechanism of alcoholic dependence, formed in the perinatal period. Journal of new medical technologies. 2018;25(3):137-141. (In Russ.)]. https://doi.org/ 10.24411/1609-2163-2018-16125.
- Карпова И.В., Бычков Е.Р., Лебедев А.А., Шабанов П.Д. Блокада орексиновых рецепторов ядра ложа конечной полоски повышает уровень серотонина только в левом гипоталамусе // Обзоры по клинической фармакологии и лекарственной терапии. – 2018. – Т. 16. – № 2. – С. 33–36. [Karpova IV, Bychkov ER, Lebedev AA, Shabanov PD. Blockade of orexin receptors in the bed nucleus of stria terminalis increases serotonin level only in the left hypothalamus. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(2):33-36. (In Russ.)]. https://doi.org/ 10.17816/RCF16233-36.
- Лебедев А.А., Хохлов П.П., Якушина Н.Д., и др. Фармакологический и биохимический анализ участия пептидной системы грелина в поведенческих проявлениях игровой зависимости у крыс // Экспериментальная и клиническая фармакология. – 2019. – Т. 82. – № 6. – С. 16–20. [Lebedev AA, Khokhlov PP, Yakushina ND, et al. Pharmacological and Biochemical Analysis of Participation of the Ghrelin Peptide System in Behavioral Manifestations of Gambling In Rats. Experimental and clinical pharmacology. 2019;82(6):16-20. (In Russ.)]. https://doi.org/ 10.30906/0869-2092-2019-82-6-16-20.
- Тиссен И.Ю., Якушина Н.Д., Лебедев А.А., и др. Эффекты антагониста OX1R рецепторов орексина А SB-408124 на компульсивное поведение и уровень тревожности после витального стресса у крыс // Обзоры по клинической фармакологии и лекарственной терапии. – 2018. – Т. 16. – № 1. – С. 34–42. [Tissen IYu, 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.)]. https://doi.org/ 10.17816/RCF16134-42.
- Якушина Н.Д., Тиссен И.Ю., Лебедев А.А., и др. Возможное участие OX1R рецепторов орексина А в компульсивном поведении и поддержании уровня тревожности после витального стресса у крыс // Вестник Смоленской государственной медицинской академии. – 2018. – Т. 17. – № 1. – С. 10–18. [Yakushina ND, Tissen IYu, Lebedev AA, et al. Probable participation of OX1R orexin A receptor in the compulsive behavior and support of the level of anxiety after vital stress in rats. Vestnik Smolenskoy gosudastvennoy meditsinskoy akademii. 2018;17(1):10-18. (In Russ.)]
- Айрапетов МИ, Сексте ЭА, Ереско СО, и др. Хроническая алкоголизация приводит к изменению уровня мРНК рецептора орексина первого типа (OX1R) в эмоциогенных структурах мозга крыс // Биомедицинская химия. – 2018. – Т. 64. – № 5. – С. 451–454. [Airapetov MI, Sekste EA, Eresko SO, et al. Chronic alcoholism influences the mRNA level of the orexin receptor type 1 (OX1R) in emotiogenic structures of the rat brain. Biomed Khim. 2018;64(5):451-454. (In Russ.)] https://doi.org/ 10.18097/PBMC20186405451.
- Aston-Jones G, Smith RJ, Sartor GC, et al. Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction. Brain Res. 2010;1314:74-90. https://doi.org/ 10.1016/j.brainres.2009.09.106.
- Boutrel B, de Lecea L. Addiction and arousal: the hypocretin connection. Physiol Behav. 2008;93(4-5):947-951. https://doi.org/ 10.1016/j.physbeh.2007.11.022.
- de Lecea L. Hypocretins and the neurobiology of sleep-wake mechanisms. Prog Brain Res. 2012;198:15-24. https://doi.org/ 10.1016/B978-0-444-59489-1.00003-3.
- Gotter AL, Roecker AJ, Hargreaves R, et al. Orexin receptors as therapeutic drug targets. Prog Brain Res. 2012;198:163-188. https://doi.org/ 10.1016/B978-0-444-59489-1.00010-0.
- Hara J, Beuckmann CT, Nambu T, et al. Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity. Neuron. 2001;30(2):345-354. https://doi.org/ 10.1016/s0896-6273(01)00293-8.
- Haynes AC, Chapman H, Taylor C, et al. Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. Regul Pept. 2002;104(1-3):153-159. https://doi.org/ 10.1016/s0167- 0115(01)00358-5.
- Koob GF. A Role for Brain Stress Systems in Addiction. Neuron. 2008;59(1):11-34. https://doi.org/ 10.1016/j.neuron.2008.06.012.
- Peyron C, Tighe DK, van den Pol AN, et al. Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems. J Neurosci. 1998;18(23):9996-10015. https://doi.org/ 10.1523/jneurosci.18-23-09996.1998.
- Roik RO, Lebedev AA, Shabanov PD. The value of extended amygdala structures in emotive effects of narcogenic with diverse chemical structure. Research Results in Pharmacology. 2019;5(3):11-19. https://doi.org/ 10.3897/rrpharmacology.5.38389.
- Sustkova-Fiserova M, Puskina N, Havlickova T, et al. Ghrelin receptor antagonism of fentanyl-induced conditioned place preference, intravenous self-administration, and dopamine release in the nucleus accumbens in rats. Addict Biol. 2019: e12845. https://doi.org/ 10.1111/adb.12845.
- Tissen IY, Lebedev AA, Tsikunov SG, Shabanov PD. Orexin A is involved in stress-induced behavior due to social isolation and psychotraumatic exposure. In Proceedings of the 26th International “Stress and Behavior” Neuroscience and Biopsychiatry Conference; Saint Petersburg, 16-19 May 2019. Saint Petersburg; 2019. p. 25-26.
- Tissen I, Kurbanov R, Hohlov K, et al. OX1R antagonist SB408124 action and extrahypothalamic CRF in rats after psychotraumatic exposure. Georgian Med News. 2019;5(290):127-131.
- Winsky-Sommerer R, Yamanaka A, Diano S, et al. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci. 2004;24(50):11439-11448. https://doi.org/ 10.1523/JNEUROSCI.3459-04.2004.
