The Chronic Treatment With 5-HT 2A Receptor Agonists Affects the Behavior and the BDNF System in Mice
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ORIGINAL PAPER
The Chronic Treatment With 5-HT2A Receptor Agonists Affects the Behavior and the BDNF System in Mice Anton S. Tsybko1 · Tatiana V. Ilchibaeva1 · Elena A. Filimonova1 · Dmitry V. Eremin1 · Nina K. Popova1 · Vladimir S. Naumenko1 Received: 23 April 2020 / Revised: 13 September 2020 / Accepted: 15 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Serotonin 5-HT2A receptors and the brain-derived neurotrophic factor (BDNF) are involved in the pathophysiology and treatment of many psychiatric diseases. However, the interaction between 5-HT2A and BDNF is still poorly understood. In the present paper, the effects of chronic treatment with mixed 5-HT2A/2C receptor agonist DOI, highly selective 5-HT2A agonists TCB-2 and 25CN-NBOH on behavior and the BDNF system have been investigated. Chronic treatment of males of C57Bl/6 mice with DOI, TCB-2 and 25CN-NBOH (1 mg/kg, i.p., 14 days) resulted in desensitization of 5-HT2A receptors. Treatment with 25CN-NBOH significantly increased startle amplitude. At the same time all used drugs failed to affect anxiety, exploratory and stereotyped behavior as well as spatial memory and learning. TCB-2 and 25CN-NBOH increased the BDNF mRNA level. All 5-HT2A agonists increased the proBDNF level but failed to alter the mature BDNF protein level. TrkB and p75NTR mRNA levels were affected by all utilized agonists. All drugs decreased the total level as well as membrane TrkB protein one indicating downregulation of TrkB receptors. All agonists decreased the membrane p75NTR protein level. Thus, we have shown for the first time that the chronic activation of the 5-HT2A receptor with agonists has affected the BDNF system almost on all levels—transcription, proBDNF production, TrkB and p 75NTR receptors’ level. The obtained data suggested possible suppression in BDNF-TrkB signaling under chronic treatment with 5-HT2A agonists. Keywords 5-HT2A receptors · BDNF system · DOI · TCB-2 · 25CN-NBOH · behavior
Introduction Mood and anxiety disorders are becoming the leading cause of disability worldwide [1–3], placing an enormous economic burden and significantly deteriorating patients’ quality of life. Over the last twenty years, the neurotrophic hypothesis of stress-related mood disorders has gained considerable popularity. This hypothesis postulates that stressrelated deficit in expression of specific neurotrophic factors (primarily the brain-derived neurotrophic factor; BDNF) in the limbic brain areas underlies mood disorders, while Anton S. Tsybko and Tatiana V. Ilchibaeva contributed equally to this work. * Anton S. Tsybko [email protected] 1
The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of Russian Academy of Sciences, Prospekt Lavrentyeva, 10, 630090 Novosibirsk, Russia
antidepressants may restore the BDNF level with consequent positive neuroplastic changes [4]. The ability to promote structural and functional neural plasticity is considered as a beneficial feature of a potent antidepressant and an
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