su-5402 and Depressive-Disorder

Basic and clinical studies report that the expression of fibroblast growth factor-2 (FGF-2) is decreased in the prefrontal cortex (PFC) of depressed subjects or rodents exposed to stress and increased following antidepressant treatment. Here, we aim to determine if 1) FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for mediating an antidepressant response behaviorally and cellularly; and 2) if the antidepressant actions of FGF-2 are mediated specifically by the PFC.. The role of FGF-2 signaling in behavioral models of depression and anxiety was tested using chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), and novelty suppressed feeding test (NSFT). We also assessed the number of bromodeoxyuridine labeled dividing glial cells in the PFC as a cellular index relevant to depression (i.e., decreased by stress and increased by antidepressant treatment).. Chronic FGF-2 infusions (intracerebroventricular) blocked the deficit in SCT caused by CUS. Moreover, the response to antidepressant treatment in the CUS/SCT and FST was abolished upon administration of an inhibitor of FGFR activity, SU5402. These results are consistent with the regulation of proliferating cells in the PFC, a portion of which are of oligodendrocyte lineage. Lastly, subchronic infusions of FGF-2 into the PFC but not into the dorsal striatum produced antidepressant-like and anxiolytic-like effects on FST and NSFT respectively.. These findings demonstrate that FGF-2/FGFR signaling is sufficient and necessary for the behavioral, as well as gliogenic, actions of antidepressants and highlight the PFC as a brain region sensitive to the antidepressant actions of FGF-2.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Bromodeoxyuridine; Depressive Disorder; Disease Models, Animal; Fibroblast Growth Factor 2; Fluoxetine; Imipramine; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neuroglia; Prefrontal Cortex; Pyrroles; Rats; Rats, Sprague-Dawley; Receptors, Fibroblast Growth Factor; Stress, Psychological