This question was addressed by assessing the effects of early life FGF2, administered the day after birth, on emotionality, hippocampal development Panobinostat concentration and gene expression (Turner et al., 2011). Remarkably, a single injection of FGF2 (20 ng/g, subcutaneously) early in life was able to alter neurogenesis in outbred animals. In adulthood, these animals exhibited a denser dentate gyrus with more

neurons, consistent with the idea that neurogenesis precedes gliogenesis in early development (Palmer et al., 1999). Moreover, when the same early life FGF2 treatment was given to high anxiety animals (bLRs), FGF2 decreased their spontaneous anxiety (Turner et al., 2011). This effect was associated with altered gene expression in the dentate gyrus. Laser capture microdissection followed by microarray analyses identified transcripts that differed between bLR-VEH and bLR-FGF2 animals. Specifically, molecules previously associated with anxiety (gad1) were decreased, whereas molecules associated with cell

survival (bcl2-like2) were increased in the high anxiety bred rats in conjunction with decreased anxiety by FGF2 treatment. Thus, early life FGF2 treatment altered the developmental trajectory of the dentate gyrus and had long-term effects on emotionality and gene expression. Most recently, a study by Duman’s group extended these findings to mice and to other models of stress (Elsayed et al., 2012). Thus, the authors reported Selleckchem Docetaxel that chronic infusion of FGF2 had antidepressant-like effects in both rats and mice. They also added site-specificity to the antidepressant effects by infusing FGF2 into the medial prefrontal cortex. Moreover, FGF2 blocked the effects of

chronic unpredictable stress (CUS) on both Metalloexopeptidase depression-like behavior, and the CUS-induced inhibition of glial proliferation. Treatment with an FGF receptor antagonist that targets all FGF receptors blocked the effects of fluoxetine on glial proliferation, as well as the effect of fluoxetine as an antidepressant. These results suggest that not only is FGF2 a sufficient antidepressant, it is also necessary for the antidepressant effects of SSRIs, although the lack of selectivity of the available FGF antagonists requires caution in the interpretation of these latter results. Moreover, the study by Elsayed et al. (2012) also hinted at relatively rapid effects of FGF2 in animal models of depression and anxiety (5 days after administration). We have also observed rapid effects of FGF2 in other paradigms. Indeed, some of the behavior and biochemical effects of FGF2 can be observed within minutes and certainly within hours, but the mechanism of these rapid effects needs further exploration. FGFR1 is required for the electrophysiological correlate of learning and memory, long-term potentiation (Zhao et al., 2007).