Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice.
Evidence from a variety of sources suggests that structural alterations in the brain, including neurogenesis, may play a role in both the pathogenesis of mood disorders and the mechanism of action of antidepressants. Previous studies have implicated both the transforming growth factor-beta (TGF-beta), and the phosphatidyl inositol-3 kinase (PI3K)-Akt pathways in the neurogenesis-promoting and behavioral properties of antidepressants. Forkhead box protein G1 (FoxG1) is a major regulator of both of these pathways, and FoxG1 heterozygous null mice (FoxG1+/-) have previously been reported to have deficits in adult hippocampal neurogenesis and behavioral abnormalities including deficits in contextual fear learning. However the role of FoxG1, if any, in the response to antidepressants has not been previously investigated.To investigate the role of the FoxG1 gene in the behavioral and neurogenic properties of antidepressants, we tested FoxG1+/- mice and littermate controls in two different rodent models of antidepressant action: the tail suspension test and the forced swim test. FoxG1+/- mice showed no response to antidepressants in either of these tests. These results suggest that normal levels of FoxG1 may be required for the behavioral response to antidepressants.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
Rebecca
R
Kinsler
Mary Morgan
MM
Taylor
Natasha M
NM
Flores
Janine J
JJ
Leffert
Robert D
RD
Beech
D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009483:Neuropsychological Tests; D013550:Swimming; D013623:Tail
D018687:Antidepressive Agents, Second-Generation; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D009419:Nerve Tissue Proteins; D005473:Fluoxetine