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Effects of antidepressant treatment on mice lacking brain‐derived neurotrophic factor expression through promoter IV
Author(s) -
Sakata Kazuko,
Mastin Joshua R.,
Duke Sean M.,
Vail Meghan G.,
Overacre Abigail E.,
Dong Brittany E.,
Jha Shanker
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12148
Subject(s) - tail suspension test , behavioural despair test , antidepressant , neurogenesis , imipramine , neurotrophic factors , brain derived neurotrophic factor , endocrinology , phenelzine , fluoxetine , psychology , medicine , neurotrophin , open field , hippocampus , pharmacology , neuroscience , chemistry , serotonin , receptor , monoamine oxidase , enzyme , biochemistry , alternative medicine , pathology
Brain‐derived neurotrophic factor ( BDNF ) is implicated in the pathophysiology of major depression; mice lacking BDNF expression through promoter IV ( BDNF ‐ KIV ) exhibit a depression‐like phenotype. We tested our hypothesis that deficits caused by promoter IV deficiency (depression‐like behavior, decreased levels of BDNF , and neurogenesis in the hippocampus) could be rescued by a 3‐week treatment with different types of antidepressants: fluoxetine, phenelzine, duloxetine, or imipramine. Each antidepressant reduced immobility time in the tail suspension test without affecting locomotor activity in the open field test in both BDNF ‐ KIV and control wild type mice, except that phenelzine increased locomotor activity in wild type mice and anxiety‐like behavior in BDNF ‐ KIV mice. The antidepressant treatments were insufficient to reverse decreased BDNF levels caused by promoter IV deficiency. No antidepressant treatment increased the hippocampal progenitors of either genotype, whereas phenelzine decreased the surviving progenitors in both genotypes. The antidepressant treatments differently affected the dendritic extension of hippocampal immature neurons: fluoxetine and imipramine increased extension in both genotypes, duloxetine increased it only in BDNF ‐ KIV mice, and phenelzine decreased it only in wild type mice. Interestingly, a saline‐only injection increased neurogenesis and dendrite extensions in both genotypes. Our results indicate that the behavioral effects in the tail suspension test by antidepressants do not require promoter IV ‐driven BDNF expression and occur without a detectable increase in hippocampal BDNF levels and neurogenesis but may involve increased dendritic reorganisation of immature neurons. In conclusion, the antidepressant treatment demonstrated limited efficacy; it partially reversed the defective phenotypes caused by promoter IV deficiency but not hippocampal BDNF levels.