%0 Journal Article
%A Borroto-Escuela, Dasiel O
%A Narváez, Manuel
%A Ambrogini, Patrizia
%A Ferraro, Luca
%A Brito, Ismel
%A Romero-Fernandez, Wilber
%A Andrade-Talavera, Yuniesky
%A Flores-Burgess, Antonio
%A Millon, Carmelo
%A Gago, Belen
%A Narvaez, Jose Angel
%A Odagaki, Yuji
%A Palkovits, Miklos
%A Diaz-Cabiale, Zaida
%A Fuxe, Kjell
%T Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.
%D 2018
%U http://hdl.handle.net/10668/12542
%X Due 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.
%K G protein-coupled receptors
%K depression
%K fibroblast growth factor receptor
%K galanin
%K heteroreceptor complexes
%K oligomerization
%K receptor tyrosine kinase
%K receptor-receptor interactions
%K serotonin 5-HT1A receptor
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