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The Effects of Nootropic Drugs on Striatal 5-HT2A-Receptors in Outbred Mice with Different Efficacy of Exploratory Behavior

https://doi.org/ 10.24411/2587-7836-2018-10023.

Abstract

Resume. The effect of subchronic administration of nootropic drugs of different structures (piracetam 200 mg/kg/day, pantocalcin 200 mg/kg/day, semax 0.6 mg/ kg/day, nooglutil 50 mg/kg/day) to mice of the outbred line 1CR on spontaneous research activity in a closed cross-maze and on the binding characteristics of 5-HT2A-receptors in striatal membranes. In experiments using [3H] (+)Ketanserin, it has been established that the mice brains exhibiting a low efficacy of exploratory behavior (LEEB) in the closed cross-maze test has a lower density of 5-HT2A receptors (Bmax = 519 ± 13 fmol/ mg , p = 0.02) in comparison with the subpopulation with high efficacy of exploratory behavior (HEEB) (639 ± 48 fmol / mg). After 5-fold administration of nootropics, only in groups with LEEB there was a significant increase in the Bmax value under the action of all investigated nootropics: piracetam (643 ± 42 fmol/mg); pantocalcine (662 ± 29 fmol/mg); semax (742 ± 29 fmol/mg) and nooglutil (1145 fmol/mg) at p = 0.01. By the Kd value, the subpopulations did not initially differ and did not undergo significant changes under the action of the drugs. The presence of serotonin-positive effects of all drugs studied in animals with initially reduced receptor density is consistent with the hypothesis of the selective, modulating nature of the nootropics action.

About the Authors

Yu. Yu. Firstova
FSBI «Zakusov Institute of Pharmacology»
Russian Federation


E. V. Vasileva
FSBI «Zakusov Institute of Pharmacology»
Russian Federation


G. I. Kovalev
FSBI «Zakusov Institute of Pharmacology»
Russian Federation


References

1. Archer T. Serotonin and fear retention in the rat. J. Сотр Physiol Psychol. 1982;96:491- 516. DOI: 10.1037/h0077897

2. Aghajanian GK, Andrade R. Electrophysiology of 5-HT receptors. In: Baumgarten HG, Gothert M., eds. Serotonergic neurons and 5-HT receptors in the CNS. Berlin: Хргіп§ег-УегІа§; 1997. p. 499- 535. DOI: 10.1007/978-3-642-60921-3_19

3. Harvey JA. Role of the Serotonin 5-HT 2A Receptor in Learning. Learning & Memory. 2003;10(5):355- 362. DOI: 10.1101/lm.60803

4. Aznar S., El-Sayed Hervig M. The 5-HT2A serotonin receptor in executive function: Implications for neuropsychiatric and neurodegenerative diseases. Aeuroscience & Biobehavioral Reviews. 2016;64:63- 82. DOI: 10.1016/j.neubiorev.2016.02.008

5. Prinssen EP, Kleven MS, Коек W. Effects of dopamine antagonists in a two way active avoidance procedure in rats: Interactions with 8-OH-DPAT, ritanserin, and prazosin. Psychopharmacology. 1996;128:191- 197. DOI: 10.1007/s002130050124

6. Luciana M., Collins PF, Depue RA. Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions. Cerebral Cortex. 1998;8:218- 226. DOI: 10.1093/cercor/8.3.218

7. Zhang C., Marek GJ. AMPA receptor involvement in 5-hydroxytryptamine 2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes. Prog. Aeuropsychopharmacol. Biol. Psychiatry. 2008;32(1):62- 71. DOI: 10.1016/j.pnpbp.2007.07.009.

8. Roth B. Irving Page Lecture: 5-HT 2A serotonin receptor biology: Interacting proteins, kinases and paradoxical regulation. Aeuropharmacology. 2011;61:348- 354. DOI: 10.1016/j.neuropharm.2011.01.012

9. Meneses A. Neurotransmitters and Memory: Cholinergic, Glutamatergic, GABAergic, Dopaminergic, Serotonergic, Signaling, and Memory. Identification of Aeural Markers Accompanying Memory. 2014;5-45. DOI: 10.1016/B978-0-12-408139-0.00002-X

10. Салимов Р.М. Оценка упорядоченности пути в процессе исследовательского поведения у мышей // Журнал высшей нервной деятельности им. И.П. Павлова. - 1988. - Т.38. - №3. - С.569- 571.

11. Ковалев Г.И. Фармакодинамика ноотропных средств. Экспериментальная и клиническая фармакология. - 2018. - Т.81. - №S. - С. 114.

12. Salimov RM, Kovalev GI. Effects of N-cholinergic drugs on behavior in the explorative cross-maze in mice: comparison with cognitive enhancers. Eur. Aeuropsychopharmacology. 2005;15(2):230- 234. DOI: 10.1016/s0924-977x(05)80455-9

13. Ковалев Г.И., Фирстова Ю.Ю., Салимов Р.М. Влияние пирацетама и ацефена на NMDA и никотиновые рецепторы мозга мы шей с различной эффективностью исследовательского поведения в крестообразном лабиринте // Экспериментальная и клиническая фармакология. - 2008. - Т.71. - №1 - С.12-17. DOI: https://doi.org/10.30906/0869-2092-2008-71-1-12-17

14. Ковалёв Г.И., Фирстова Ю.Ю., Салимов Р.М., и др. Механизмы избирательного действия Семакса при когнитивном дефиците у мышей // Психиатрия. - 2010. - Т3. - №45. - С.23- 28.

15. Фирстова Ю.Ю., Абаимов Д.А., Капица И.Г., и др. Влияние скополамина и ноотропного препарата фенотропила на рецепторы нейромедиаторов мозга крыс в тесте условного рефлекса пассивного избегания (УРПИ) // Нейрохимия. - 2011. - Т.28. - №2. - С.130-141.

16. Seger CA. The basal ganglia in human learning. The Aeuroscientist. 2006;12(4):285- 290. DOI: 10.1177/1073858405285632

17. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. / Под ред. Миронова А.Н. - М.: Гриф и К.; 2012.

18. Miguelez C., Morera-Herreras T., Torrecilla M., et al. Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson’s disease. Frontiers in Aeural Circuits. 2014;8(21):1-9. DOI: 10.3389/fncir.2014.00021

19. Leysen JE, Niemegeers CJ, Van Nueten JM, et al. [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution, and functional role. Mol. Pharmacol. 1982;21(2):301-314.

20. Hasselbalch SG, Madsen K., Svarer C., et al. Reduced 5-HT 2A receptor binding in patients with mild cognitive impairment. Aeurobiology of aging. 2008;29:1830- 1838. DOI: 10.1016/j.neurobiolaging.2007.04.011

21. Фирстова Ю.Ю., Долотов О.В., Кондрахин Е.А., и др. Влияние ноотропных препаратов на уровень BDNF в гиппокампе и коре мозга мышей с различной эффективностью исследовательского поведения // Экспериментальная и клиническая фармакология. - 2009. - Т72. - №6. - С.3-6.


Review

For citations:


Firstova Yu.Yu., Vasileva E.V., Kovalev G.I. The Effects of Nootropic Drugs on Striatal 5-HT2A-Receptors in Outbred Mice with Different Efficacy of Exploratory Behavior. Pharmacokinetics and Pharmacodynamics. 2018;(3):42-47. (In Russ.) https://doi.org/ 10.24411/2587-7836-2018-10023.

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ISSN 2587-7836 (Print)
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