title: Antidepressant effects of fibroblast growth factor-2 in behavioral and cellular models of depression.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, USA.
authors.forename: Maha
authors.initials: M
authors.lastname: Elsayed
authors.forename: Mounira
authors.initials: M
authors.lastname: Banasr
authors.forename: Vanja
authors.initials: V
authors.lastname: Duric
authors.forename: Neil M
authors.initials: NM
authors.lastname: Fournier
authors.forename: Pawel
authors.initials: P
authors.lastname: Licznerski
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D005473:Fluoxetine; D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine; D007099:Imipramine