Anton V. Malyshev, Vsevolod V. Pavshintcev, Nikita A. Mitkin, Iuliia A. Sukhanova, Vasilina R. Gedzun, Alexander S. Zlobin, Igor I. Doronin, Gennady A. Babkin, Tomi K. Sawyer
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Rodent behavioral screening in the open field and elevated plus maze revealed increased locomotor activity in both tests after acute LCGM-10 treatment, supported by further analysis of home cage spontaneous locomotor activity (SLA). The stimulating effect of a single LCGM-10 administration on SLA was evident up to 60 min after administration and was not accompanied by hypokinetic rebound observed for caffeine. According to our results, LCGM-10 has therapeutic potential to treat hypo- and dyskinesias of various etiologies. Further investigation of LCGM-10 effects in the delay discounting model of impulsive choice in rats revealed reduced trait impulsivity after single and chronic administrations, suggesting potential implication for attention deficit hyperactivity disorder, obsessive compulsive disorder, and addictions.","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models\",\"authors\":\"Anton V. Malyshev, Vsevolod V. Pavshintcev, Nikita A. Mitkin, Iuliia A. Sukhanova, Vasilina R. Gedzun, Alexander S. Zlobin, Igor I. Doronin, Gennady A. Babkin, Tomi K. Sawyer\",\"doi\":\"10.3389/fnbeh.2024.1333258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"We employed a structural bioinformatics approach to develop novel peptides with predicted affinity to the binding site for negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5). Primary screening in zebrafish (<jats:italic>Danio rerio</jats:italic>) revealed a stimulatory effect of two peptides, LCGM-10 and LCGM-15. Target validation studies using calcium ion flux imaging and a luciferase reporter assay confirmed mGluR5 as the target. LCGM-10 showed greater potency than LCGM-15; it was comparable to that of the mGluR5 NAM 2-methyl-6-(phenylethynyl) pyridine (MPEP). Rodent behavioral screening in the open field and elevated plus maze revealed increased locomotor activity in both tests after acute LCGM-10 treatment, supported by further analysis of home cage spontaneous locomotor activity (SLA). The stimulating effect of a single LCGM-10 administration on SLA was evident up to 60 min after administration and was not accompanied by hypokinetic rebound observed for caffeine. According to our results, LCGM-10 has therapeutic potential to treat hypo- and dyskinesias of various etiologies. Further investigation of LCGM-10 effects in the delay discounting model of impulsive choice in rats revealed reduced trait impulsivity after single and chronic administrations, suggesting potential implication for attention deficit hyperactivity disorder, obsessive compulsive disorder, and addictions.\",\"PeriodicalId\":12368,\"journal\":{\"name\":\"Frontiers in Behavioral Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-02-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Behavioral Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnbeh.2024.1333258\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Behavioral Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnbeh.2024.1333258","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models
We employed a structural bioinformatics approach to develop novel peptides with predicted affinity to the binding site for negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5). Primary screening in zebrafish (Danio rerio) revealed a stimulatory effect of two peptides, LCGM-10 and LCGM-15. Target validation studies using calcium ion flux imaging and a luciferase reporter assay confirmed mGluR5 as the target. LCGM-10 showed greater potency than LCGM-15; it was comparable to that of the mGluR5 NAM 2-methyl-6-(phenylethynyl) pyridine (MPEP). Rodent behavioral screening in the open field and elevated plus maze revealed increased locomotor activity in both tests after acute LCGM-10 treatment, supported by further analysis of home cage spontaneous locomotor activity (SLA). The stimulating effect of a single LCGM-10 administration on SLA was evident up to 60 min after administration and was not accompanied by hypokinetic rebound observed for caffeine. According to our results, LCGM-10 has therapeutic potential to treat hypo- and dyskinesias of various etiologies. Further investigation of LCGM-10 effects in the delay discounting model of impulsive choice in rats revealed reduced trait impulsivity after single and chronic administrations, suggesting potential implication for attention deficit hyperactivity disorder, obsessive compulsive disorder, and addictions.
期刊介绍：
Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.
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