Antidepressant Effects of Fibroblast Growth Factor-2 in Behavioral and Cellular Models of Depression

• Published in: Biological psychiatry (1969) Vol. 72; no. 4; pp. 258 - 265
• Main Authors: Elsayed, Maha, Banasr, Mounira, Duric, Vanja, Fournier, Neil M., Licznerski, Pawel, Duman, Ronald S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.08.2012; Elsevier
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Antidepressants; Antidepressive Agents - pharmacology; Biological and medical sciences; Bromodeoxyuridine; chronic unpredictable stress; Depression; Depressive Disorder - drug therapy; Disease Models, Animal; Fibroblast Growth Factor 2 - metabolism; Fibroblast Growth Factor 2 - pharmacology; Fibroblast Growth Factor 2 - therapeutic use; fibroblast growth factor-2; Fluoxetine - pharmacology; Imipramine - pharmacology; Immunohistochemistry - methods; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mood disorders; Neuroglia - drug effects; Neuroglia - metabolism; Neuropharmacology; NG2-glia; Pharmacology. Drug treatments; prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychiatric/Mental Health; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyrroles - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Stress, Psychological - metabolism; fibroblast growth factor-2; chronic unpredictable stress; NG2-glia; depression; Antidepressants; prefrontal cortex; Mood disorder; Fibroblast growth factor; Psychotropic; Neuroglia; Central nervous system; Depression; Prefrontal cortex; Stress; Encephalon; Chronic; Behavioral analysis; Antidepressant agent
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2012.03.003

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.