BEHAVIORAL EFFECTS OF FLUOXETINE IN AN ANIMAL MODEL OF ANXIETY/DEPRESSION ARE MEDIATED BY BOTH NEUROGENESIS-DEPENDENT AND INDEPENDENT MECHANISMS

By D. David, B. Samuels, Q. Rainer, Jing-wen Wang, D. Marsteller, Indira Mendez, M. Drew, Douglas A. Craig, B. Guiard, J. Guilloux and 6 more. 2009

1,227 citations recorded by the source corpus.

SUMMARY Understanding the physiopathology of affective disorders and their treatment relies on the availability of experimental models that accurately mimic aspects of the disease. Here we describe a mouse model of an anxiety/depressive-like state induced by chronic corticosterone treatment. Furthermore, chronic antidepressant treatment reversed the behavioral dysfunctions and the inhibition of hippocampal neurogenesis induced by corticosterone treatment. In corticosterone-treated mice where hippocampal neurogenesis is abolished by X-irradiation, the efficacy of fluoxetine is blocked in some but not all behavioral paradigms, suggesting both neurogenesis-dependent and independent mechanisms of antidepressant actions. Finally, we identified a number of candidate genes, the expression of which is decreased by chronic corticosterone and normalized by chronic fluoxetine treatment selectively in the hypothalamus. Importantly, mice deficient in one of these genes, β-arrestin 2, displayed a reduced response to fluoxetine in multiple tasks, suggesting that β-arrestin signaling is necessary for the antidepressant effects of fluoxetine.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Developmental Neuroscience

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Citations in the corpus

New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “However, there is no direct evidence that adult neurogenesis is required for emotional regulation, although it can mediate the efficacy of antidepressants under certain condition”
Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior (2012, background): “A number of antidepressants have been shown to increase neurogenesis in the brain, and some of the behavioral effects of these drugs are dependent on the stimulation of neurogenesis (Duman and Monteggia, 2006; David et al, 2009).”
Effects of adult-generated granule cells on coordinated network activity in the dentate gyrus (2010, background): “X-irradiation are similar in C57 and 129 strains of mice (David et al., 2009).”
Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders (2014, neutral): “Nevertheless, adult neurogenesis is not necessary for all antidepressant responses in animal models, suggesting the existence of neurogenesisdependent and -independent mechanisms of antidepressant action, at least in rodent depression models (David et al., 2009).”
The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity (2010, background): “Essentially all of these animal models are unsatisfactory in one way or another (Krishnan and Nestler, 2008; David et al., 2009).”
The current state of the neurogenic theory of depression and anxiety. (2015, background): “In a subsequent study using stressed mice, some, but not all, of the behavioral effects of fluoxetine was AHN dependent [59].”
Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding (2016, neutral): “…have implicated abGCs in memory formation (Zhao et al., 2008); stress and anxiety (Snyder et al., 2011); responses to antidepressant treatments (David et al., 2009; Santarelli et al., 2003); and, most recently, in behaviors requiring contextual discrimination, consistent with a role in pattern…”
Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors (2015, methodology): “We have previously observed that our model of chronic CORT treatment has no effect on baseline CORT levels (unpublished data), however, does diminish the elevated levels of CORT produced in response to acute swim stress, as compared with control animals (David et al, 2009).”