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Crh receptor priming in the bed nucleus of the stria terminalis (BNST) induces tph2 gene expression in the dorsomedial dorsal raphe nucleus and chronic anxiety.

Authors
  • Donner, Nina C1
  • Davies, Sofia M2
  • Fitz, Stephanie D3
  • Kienzle, Drake M4
  • Shekhar, Anantha5
  • Lowry, Christopher A6
  • 1 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: [email protected]
  • 2 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: [email protected]
  • 3 Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: [email protected] , (India)
  • 4 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA. Electronic address: [email protected]
  • 5 Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: [email protected] , (India)
  • 6 Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine & Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Veterans Health Administration, Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Rocky Mountain Regional Veterans Affairs Medical Center (RMRVAMC), Aurora, CO 80045, USA; Military and Veteran Microbiome: Consortium for Research and Education, Aurora, CO 80045, USA. Electronic address: [email protected]
Type
Published Article
Journal
Progress in neuro-psychopharmacology & biological psychiatry
Publication Date
Jan 10, 2020
Volume
96
Pages
109730–109730
Identifiers
DOI: 10.1016/j.pnpbp.2019.109730
PMID: 31415826
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The bed nucleus of the stria terminalis (BNST) is a nodal structure in neural circuits controlling anxiety-related defensive behavioral responses. It contains neurons expressing the stress- and anxiety-related neuropeptide corticotropin-releasing hormone (Crh) as well as Crh receptors. Repeated daily subthreshold activation of Crh receptors in the BNST is known to induce a chronic anxiety-like state, but how this affects neurotransmitter-relevant gene expression in target regions of the BNST is still unclear. Since the BNST projects heavily to the dorsal raphe nucleus (DR), the main source of brain serotonin, we here tested the hypothesis that such repeated, anxiety-inducing activation of Crh receptors in the BNST alters the expression of serotonergic genes in the DR, including tph2, the gene encoding the rate-limiting enzyme for brain serotonin synthesis, and slc6a4, the gene encoding the serotonin transporter (SERT). For 5 days, adult male Wistar rats received daily, bilateral, intra-BNST microinjections of vehicle (1% bovine serum albumin in 0.9% saline, n = 11) or behaviorally subthreshold doses of urocortin 1 (Ucn1, n = 11), a potent Crh receptor agonist. Priming with Ucn1 increased tph2 mRNA expression selectively within the anxiety-related dorsal part of the DR (DRD) and decreased social interaction (SI) time, a measure of anxiety-related defensive behavioral responses in rodents. Decreased social interaction was strongly correlated with increased tph2 mRNA expression in the DRD. Together with previous studies, our data are consistent with the hypothesis that Crh-mediated control of the BNST/DRD-serotonergic system plays a key role in the development of chronic anxiety states, possibly also contributing to stress-induced relapses in drug abuse and addiction behavior. Copyright © 2019 Elsevier Inc. All rights reserved.

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