Borroto-Escuela, Dasiel ONarváez, ManuelAmbrogini, PatriziaFerraro, LucaBrito, IsmelRomero-Fernandez, WilberAndrade-Talavera, YunieskyFlores-Burgess, AntonioMillon, CarmeloGago, BelenNarvaez, Jose AngelOdagaki, YujiPalkovits, MiklosDiaz-Cabiale, ZaidaFuxe, Kjell2023-01-252023-01-252018-06-03http://hdl.handle.net/10668/12542Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A⁻FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A⁻FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A⁻5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1⁻15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1⁻GalR2⁻5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/G protein-coupled receptorsdepressionfibroblast growth factor receptorgalaninheteroreceptor complexesoligomerizationreceptor tyrosine kinasereceptor-receptor interactionsserotonin 5-HT1A receptorAnimalsDepressionProtein BindingRaphe NucleiRats, Sprague-DawleyReceptor, Fibroblast Growth Factor, Type 1Receptor, Serotonin, 5-HT1ASerotoninresearch article29865267open access10.3390/molecules230613411420-3049PMC6099659https://www.mdpi.com/1420-3049/23/6/1341/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099659/pdf