title: FGFR1-5-HT1A Heteroreceptor Complexes: Implications for Understanding and Treating Major Depression.
abstract: The serotonin and neurotrophic factor hypotheses of depression are well known. The discovery of brain fibroblast growth factor receptor 1 (FGFR1)-5 hydroxytryptamine receptor 1A (5-HT1A) heteroreceptor complexes, and their enhancement of neuroplasticity, offers an integration of these hypotheses at the molecular level. They were first described in the hippocampus and later in midbrain 5-HT neurons, where these heterocomplexes are enriched in 5-HT1A autoreceptors. Combined FGF2 and 5-HT1A agonist treatment increased the formation of these heterocomplexes and the facilitatory allosteric receptor-receptor interactions within them led to the enhancement of FGFR1 signaling and was associated with the development of antidepressant effects. We discuss these findings with regard to a theory of motifs critically involved in these interactions and suggest that these complexes represent novel targets for antidepressants.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Russian Academy of Sciences, Saint Petersburg Institute for Informatics and Automation, Saint Petersburg, Russia.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Tarakanov
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. Electronic address: Kjell.Fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D009488:Neurosciences / Q000639:trends*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: 5-HT1A receptor; allosteric receptor–receptor interactions; depression; fibroblast growth factor receptor 1; heteroreceptor complexes; neural plasticity