Serotonin receptor agonist treatment induces transactivation of fibroblast growth factor receptor-1 (FGFR1) tyrosine kinase in the rat hippocampal neurons

Over the past decade, many examples of activation of receptor tyrosine kinases in response to G-protein coupled receptor signaling have been reported, indicating that there are alternative modes of receptor tyrosine kinase activation (transactivation) in the absence of neurotrophic factor binding. In the present work, we aimed to examine if 5-HT receptor subtype activation may induce fibroblast growth factor receptor-1 (FGFR1) phosphorylation through transactivation of tyrosine kinase. The study has been performed in young adult rats treated with the selective 5-HT1A receptor agonist 8-OHDPAT at the dose of 0.4 mg/kg/i.p.. FGFR1 phosphorylation was evaluated by immunoprecipitation and western blotting in a time-course study ranging between 15 min and 24h. Among the brain regions, target of the 5-HT innervations, examined in this study (cingulate and frontal cortices, and the hippocampus), only in the hippocampus the FGFR1 phosphorylation was found upregulated 24 h following 8-OH-DPAT treatment. This FGFR1 activation was independent of its ligand FGF-2 changes, and using primary cultures of hippocampal neurons the FGFR1 transactivation by 5-HT receptors was further defined. The existence of FGFR1 transactivation in response to 5-HT receptor activation will increase our understanding the mechanisms of antidepressant drug effects, since 5-HT receptors have been implicated in anxiety and depression.