Article

Widespread hypothalamic-pituitary-adrenocortical axis-relevant and mood-relevant effects of chronic fluoxetine treatment on glucocorticoid receptor gene expression in mice

Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.
European Journal of Neuroscience (Impact Factor: 3.67). 03/2010; 31(5):892-902. DOI: 10.1111/j.1460-9568.2010.07131.x
Source: PubMed

ABSTRACT Tricyclic antidepressants (TCAs) have been used to treat melancholic depression, which has been associated with elevated hypothalamic-pituitary-adrenocortical (HPA) axis activity, whereas patients suffering from atypical depression, which is often associated with decreased HPA axis activity, show preferential responsiveness to monoamine oxidase inhibitors (MAOIs). We previously reported drug-specific effects of the TCA imipramine and the MAOI phenelzine on HPA axis-relevant endpoints in mice that may explain differential antidepressant responses in melancholic vs. atypical depression. However, selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in both melancholic and atypical depression. We therefore hypothesized that SSRIs would share HPA axis-related effects with either TCAs or MAOIs. To test this hypothesis, we measured HPA axis-relevant gene expression in male C57BL/6 mice treated for 5 weeks with 10 mg/kg/day fluoxetine. To control for potential fluoxetine-induced changes in glucocorticoid secretion, mice were adrenalectomized and given fixed levels of glucocorticoids. Fluoxetine decreased glucocorticoid receptor (GR) gene expression in the prefrontal cortex, amygdala, locus coeruleus and dorsal raphé nucleus, and increased locus coeruleus tyrosine hydroxylase and dorsal raphé nucleus tryptophan hydroxylase-2 (TPH2) gene expression. These results resembled those that we previously reported for MAOI treatment, but included decreases in GR and increases in TPH2 gene expression in the dorsal raphé nucleus that were induced by TCAs but not MAOIs. Correlating with inhibitory effects on central amygdala GR gene expression, fluoxetine also decreased amygdala corticotropin-releasing hormone gene expression, an effect not previously observed with MAOIs or TCAs. These actions may be relevant to the efficacy of SSRIs in treating a range of depression and anxiety disorders.

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    • "in cells, while VMAT2 is colocalized with TH enzyme (Tillinger et al. 2010). A subpopulation of chromogranin A -expressing chromaffin cells of the adrenal medulla also express VMAT2 (Weihe et al. 1994). Chromogranins are highly efficient systems directly involved in monoamine accumulation and in the exocytotic release of catecholamines (Borges et al. 2010)."
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    Anais da Academia Brasileira de Ciências 03/2015; DOI:10.1590/0001-3765201520130400 · 0.88 Impact Factor
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    • "inhibitory effects of antidepressant treatment on HPA activity have been reported, the literature is not consistent in this regard [23] [25] [27]. Because our previous data indicated that antidepressant effects on PFC GR expression were distributed across different PFC subdivisions [6] [7], we did not initially target individual regions of the prefrontal cortex. Selective knockdown of infralimbic vs. prelimbic PFC GR was reported during the completion of the current experiments to have differential effects on emotional behavior and HPA activity, with only infralimbic GR loss increasing depression-like behavior and augmenting the impact of chronic stress on HPA responses to a novel stimulus [11]. "
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    • "Starting at the level of the paraventricular nucleus (PVN) in the hypothalamus, male mice acutely treated with fluoxetine (10 mg/kg) exhibited no changes in arginine vasopressin (Avp), oxytocin (Oxt) and CRF mRNA expression , but female wild-type animals showed increased PVN Avp and Oxt mRNA levels (Stewart et al., 2008). Upon chronic fluoxetine treatment , amygdala CRF gene expression was decreased (Heydendael & Jacobson, 2010), and Brady et al. (1992) observed that chronic fluoxetine (5 mg/kg, i.p.) treatment for 2–8 weeks decreased CRF mRNA levels by 30–48% in the PVN of the hypothalamus. The decreases occurred at 8 weeks but not at 2 weeks. "
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