, 1997, 1999). Moreover, social defeat has ethological validity, in that it mimics some of the physiological and anhedonic aspects of depression in humans. This study focused on the hippocampus, as postmortem studies pointed to this brain

region as the most altered by MDD (unpublished observations). Moreover, this is an area that is critical in the biology of “stress-related disorders,” including MDD, anxiety, and posttraumatic stress disorder (PTSD). For example, human brain imaging studies have shown that the volume of the human hippocampus is negatively correlated with Selleck BIBW2992 PTSD (Gilbertson et al., 2002), consistent with the view that this area is highly responsive to stress-related disorders. This work, in fact, suggested

that hippocampal volume may be a predisposing factor in PTSD. Thus, the hippocampal size of the twin who had not been exposed to combat predicted the magnitude of PTSD in the combat twin. Since FGF2 can control the development and size of the hippocampus (Ohkubo et al., 2004), it was logical to assess FGF2 expression in this region follow a social stress animal model. It should also be mentioned that neuroimaging studies have shown a reduced hippocampal volume in depressed subjects (Campbell et al., 2004). However, it remains unclear whether this is a result of stress and an antecedent to depression or a consequence of having the disorder. Following repeated social defeat stress, the expression selleck of FGF2, as well as one of its receptors, FGFR1, was decreased in the hippocampus (Turner et al., 2008a), suggesting the hypothesis that the observed decrease in FGF2 both in human MDDs ADP ribosylation factor and an animal model may contribute to the affective changes accompanying depression. Could FGF2 be “an endogenous antidepressant,”

and could its suppression, therefore, contribute to the negative affect of depressed humans? This hypothesis was tested by administering FGF2 intracerebroventricularly to adult rats to ascertain its potential antidepressant-like effects. Following both acute and chronic administration and across multiple tests of depression-like behavior, such as the forced swim test and novelty-suppressed feeding, FGF2 proved to have antidepressant properties (Turner et al., 2008c). Surprisingly, FGFR1 expression was also increased by the FGF2 treatment. This suggested that FGF2 can prime its own receptor and further amplify the effects of its administration. Moreover, other ligands known to bind to and activate FGF receptors, such as neural cell adhesion molecule (NCAM), also decreased depression-like behavior following acute intracerebroventricular administration (Turner et al., 2008c).