RT Journal Article
T1 FGFR1-5-HT1A Heteroreceptor Complexes: Implications for Understanding and Treating Major Depression
A1 Borroto-Escuela, Dasiel O.
A1 Tarakanov, Alexander O.
A1 Fuxe, Kjell
K1 Receptores de neurotransmisores
K1 Depresión
AB 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. 5-HT1A receptor is a 5-HT receptor subtype, which binds the endogenous transmitter 5-hydroxytryptamine. In the brain it participates in mediating antidepressant effects of classical antidepressant drugs and of serotonin selective reuptake inhibitors.FGFR1 is a receptor tyrosine kinase, the ligands of which are specific members of the fibroblast growth factor family. One of its ligands, FGF2, is shown to produce antidepressant-like effects.FGFR1-5-HT1A heteroreceptor complexes were recently discovered in the brain. In these heterocomplexes, agonist coactivation markedly enhanced FGFR1 signaling leading to increased neuroplasticity and antidepressant-like actions.The FGFR1-5-HT1A heteroreceptor complex represents a new promising target for antidepressant drugs including combined treatment with FGF2 and 5-HT1A agonists in major depression.
PB Elsevier
SN 01662236
YR 2016
FD 2016-01-01
LK https://hdl.handle.net/10630/45018
UL https://hdl.handle.net/10630/45018
LA eng
NO FGFR1–5-HT1A Heteroreceptor Complexes: Implications for Understanding and Treating Major Depression Borroto-Escuela, Dasiel O. et al. Trends in Neurosciences, Volume 39, Issue 1, 5 - 15
NO Swedish Medical Research Council (Sweden)
NO AFA Försäkring (Suecia)
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 25 feb 2026