Cited by 117Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

Regulation of corticotropin-releasing factor neuronal systems and hypothalamic-pituitary-adrenal axis activity by stress and chronic antidepressant treatment

Stout, Steven C., Owens, Michael J., Nemeroff, Charles B.·2002·The Journal of Pharmacology and Experimental Therapeutics

Abstract

In a series of experiments, we tested the hypothesis that chronic antidepressant drug administration reduces the synaptic availability of corticotropin-releasing factor (CRF) through one or more effects on CRF gene expression or peptide synthesis. We also determined whether effects of acute or chronic stress on CRF gene expression or peptide concentration are influenced by antidepressant drug treatment. Four-week treatment with venlafaxine, a dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor, and tranylcypromine, a monoamine oxidase inhibitor, resulted in an attenuation of acute stress-induced increases in CRF heteronuclear RNA (hnRNA) synthesis in the paraventricular nucleus (PVN). Trends toward the same effect were observed after treatment with the 5-HT reuptake inhibitor fluoxetine, or the NE reuptake inhibitor reboxetine. CRF mRNA accumulation in the PVN during exposure to chronic variable stress was attenuated by concurrent antidepressant administration. Basal CRF hnRNA and mRNA expression were not affected by antidepressant treatment in the PVN or in other brain regions examined. Chronic stress reduced CRF concentrations in the median eminence, but there were no consistent effects of antidepressant drug treatment on CRF, serum corticotropin, or corticosterone concentrations. CRF receptor expression and basal and stress-stimulated HPA axis activity were unchanged after antidepressant administration. These results suggest that chronic antidepressant administration diminishes the sensitivity of CRF neurons to stress rather than alters their basal activity. Additional studies are required to elucidate the functional consequences and mechanisms of this interaction.

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Crossref · 10.1124/jpet.300.3.1085

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  • Antidepressant treatment normalizes expression of CRF and CRF1 receptors in association with remission of depression.

    “Interestingly, antidepressant treatment normalizes expression of CRF and CRF 1 receptors in association with remission of depression [329,344,346].”

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Authors
Stout, S. C., Owens, M. J., & Nemeroff, C. B.
Affiliations
Emory University (US)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2002-03
Volume
300
Issue
3
Pages
1085-1092
ISSN
0022-3565 (ISSN-L)
OpenAlex
W2154085228
Cited by
117
References
36
Citations by year
2025: 1 · 2024: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 4
FWCI
3.99
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R01MH042088, P50MH058922, MH58922, MH42088)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, chronic stress, chronic antidepressant treatment, venlafaxine, tranylcypromine, fluoxetine, reboxetine, paraventricular nucleus, chronic variable stress, CRF neurons, monoamine oxidase inhibitors, serotonin reuptake inhibitors, norepinephrine reuptake inhibitors
MeSH terms
Adrenocorticotropic Hormone, Animals, Antidepressive Agents, Autoradiography, Corticotropin-Releasing Hormone, Hypothalamo-Hypophyseal System, Immobilization, Male, Neurons, Pituitary-Adrenal System, Radioimmunoassay, RNA Processing, Post-Transcriptional, RNA, Messenger, Stress, Psychological, Swimming, RNA, Antisense, Rats, Sprague-Dawley, In Situ Hybridization, Receptors, Corticotropin-Releasing Hormone, Rats

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