{"doi":"10.3389/fnbeh.2015.00065","title":"Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome","abstract":null,"journal":"Frontiers in Behavioral Neuroscience","year":2015,"id":658508,"datarank":0.5955437870328184,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":0.0,"self_endowment_contribution":0.5955437870328184,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1719033,"name":"Lara M. Sardone","orcid":null,"position":1,"is_corresponding":false},{"id":439811,"name":"Enza Lacivita","orcid":"0000-0003-2443-1174","position":2,"is_corresponding":false},{"id":439817,"name":"Marcello Leopoldo","orcid":"0000-0001-8401-2815","position":3,"is_corresponding":false},{"id":439816,"name":"Lucia Ciranna","orcid":"0000-0003-0274-6095","position":4,"is_corresponding":false},{"id":439814,"name":"Lara Costa","orcid":"0000-0002-2465-8080","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome","abstract":"Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome.","is_dataset_classified":null,"base_score":3.970291913552122,"endowment":3.970291913552122,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25814945","pmcid":"PMC4357247","openalex_id":"https://openalex.org/W2082152632","authors":[],"funders":[{"funder_name":"Telethon","grant_id":"GGP13145","title":null}],"total_grants":1,"fwci":4.498,"citation_percentile":0.9493129,"influential_citations":0,"citation_trend":[{"year":2015,"count":1},{"year":2016,"count":4},{"year":2017,"count":6},{"year":2018,"count":9},{"year":2019,"count":6},{"year":2020,"count":4},{"year":2021,"count":6},{"year":2022,"count":5},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fnbeh.2015.00065/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fnbeh.2015.00065/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3389/fnbeh.2015.00065","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25814945","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4357247","host_type":"repository"},{"url":"https://doaj.org/article/9b4e7149815241e7b71091548dd3a32b","host_type":"repository"},{"url":"http://hdl.handle.net/11586/179439","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4357247","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4357247?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genetics and Neurodevelopmental Disorders","Nuclear Receptors and Signaling","Autism Spectrum Disorder Research"],"mesh_terms":[],"keywords":["Metabotropic glutamate receptor","Long-term depression","Metabotropic receptor","Receptor","Glutamate receptor","Metabotropic glutamate receptor 5","Agonist","Chemistry","FMR1","Synaptic plasticity","Neuroscience","Metabotropic glutamate receptor 1","Biology","Pharmacology","AMPA receptor","Biochemistry","Hippocampus","Fragile X Syndrome","5-Ht7","Mglur-ltd","5-Ht7r Agonists"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T04:27:04.592338Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}