[Abstract Title]. - Society for Neuroscience

zone, which is regarded as a neurogenic niche for adult hippocampal neurogenesis; importantly
FLX treatment did not counteract this effect. At the same time FLX normalized the stressinduced
reduction in adult neurogenesis, suggesting that the effect of FLX on adult neurogenesis
is independent from the vascular niche.
Disclosures: B. Czeh , None; E. Fuchs, None.
Poster
255. Mood Disorders: Animal Models and Treatment Effects II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 255.11/Y26
Topic: C.15.f. Affective disorders: Pathology
Support: NARSAD
Title: Fluoxetine shares aspects of TCA and MAOI effects on factors relevant to hypothalamicpituitary-adrenal
axis activity: could this explain broad efficacy of SSRIs?
Authors: *W. A. HEYDENDAEL, L. JACOBSON;
Ctr. for Neuropharmacol & Neurosci, Albany Med. Coll, Albany, NY
Abstract: Abnormally high or low levels of glucocorticoids caused by dysregulation of the
hypothalamic-pituitary-adrenal (HPA) axis can affect mood and may add to depression
symptoms. Tricyclic antidepressants (TCA) have been used to treat forms of depression with
elevated HPA activity, while patients suffering from atypical depression, which is often
associated with decreased HPA activity, show a preferential responsiveness to monoamine
oxidase inhibitors (MAOI). However, selective serotonin reuptake inhibitors (SSRIs) appear to
be effective in both melancholic and atypical depression. Our lab has previously shown
differential effects of the TCA imipramine and the MAOI phenelzine on HPA activity and HPArelevant
factors. Because SSRIs can be effective for many forms of depression, we hypothesized
that the SSRI fluoxetine would have effects that would be shared with either TCA or MAOI. To
test this hypothesis, we measured gene expression for HPA-relevant factors such as
glucocorticoid receptors (GR), mineralocorticoid receptors (MR), locus coeruleus tyrosine
hydroxylase (TH) dorsal raphé tryptophan hydroxylase (TPH2), and amygdala corticotropinreleasing
hormone (CRH) in male C57BL/6 mice treated chronically with fluoxetine (10 mg/kg/d
ip for 5 weeks). Mice were sham-adrenalectomized or adrenalectomized and given fixed
glucocorticoid levels to control for any fluoxetine-induced changes in glucocorticoid secretion
that might alter GR and MR expression via autoregulation. Fluoxetine had no effect on MR
expression in the brain regions examined. However, fluoxetine did decrease GR expression in