Moreover, combining FGF-2 and 5-HT1A agonist synergistically enhanced both receptor signaling and cell differentiation, suggesting a trophic role in the serotonergic neurons (Borroto-Escuela et al., 2012b). Given the large literature on 5HT1A receptor signaling (Hannon and Hoyer, 2008), and its role in mediating the mode of action of antidepressants and in the regulation of emotional responsiveness (Blier and Abbott, 2001; Blier DNA Damage inhibitor and Ward, 2003), the molecular interaction between these two systems opens up exciting avenues

for understanding the biology and pathophysiology of affect and mood. In addition, since both FGFR1 and 5HT1A receptors are known to be present on neural stem cells, their interplay in modulating neurogenesis, e.g., upon antidepressant treatment or with environmental complexity or exercise, is of great interest. These two examples of interaction with G-Protein coupled receptors greatly expand the range of potential influence of the FGF system on neuronal signaling and the control of growth and differentiation. Such interactions might exist in other brain regions, and possibly with other G protein-coupled receptors, and couple the FGF control of neuroplasticity more directly to the actions of specific neurotransmitters. The body of work summarized

here underscores the surprising role of the FGF family not only in controlling neural development and neuroplasticity, but also in modulating many facets of emotional and motivated behavior. Equally notable is the ABT-199 datasheet fact that this modulation occurs

in multiple time domains, with early effects lasting into adult life, but also with evidence for “on-line” control of signaling and behavioral responsiveness during adulthood. mafosfamide It should be mentioned that other growth factors, such as BDNF and IGF-1, have similar neuromodulatory effects as FGF2. For example, both molecules promote neurogenesis and act as antidepressants (Anderson et al., 2002; Hoshaw et al., 2005; Schmidt and Duman, 2010). BDNF is also upregulated following antidepressant drug treatment and has long-lasting effects on hippocampal function (Monteggia et al., 2004; Nibuya et al., 1995). However, FGF2 has effects on glial cells, specifically astrocytes, which have not been shown for BDNF or IGF-1 (Numakawa et al., 2011). One of these functions includes upregulating microRNAs, where BDNF and IGF-1 failed to do so. Given that depression may be related to a perturbation in glia, this may represent a significant difference between growth factor families (Bernard et al., 2011; Choudary et al., 2005). Finally, FGF receptors can interact with other neurotransmitters, and this has the potential for FGF ligands to have multiple and rapid cellular and behavioral effects. The FGF family appears to reside at the interface of genetic, developmental, environmental, and experiential regulation of mood, affect, and addiction.