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Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience

The noradrenergic nucleus locus coeruleus is a key component of the stress circuitry of the brain. During stress, the neuropeptide corticotropin-releasing factor (CRF) is secreted onto LC, increasing LC output and norepinephrine concentration in the brain, which is thought to promote anxiety-like be...

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Autores principales: Tkaczynski, John A., Borodovitsyna, Olga, Chandler, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320195/
https://www.ncbi.nlm.nih.gov/pubmed/35884666
http://dx.doi.org/10.3390/brainsci12070860
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author Tkaczynski, John A.
Borodovitsyna, Olga
Chandler, Daniel J.
author_facet Tkaczynski, John A.
Borodovitsyna, Olga
Chandler, Daniel J.
author_sort Tkaczynski, John A.
collection PubMed
description The noradrenergic nucleus locus coeruleus is a key component of the stress circuitry of the brain. During stress, the neuropeptide corticotropin-releasing factor (CRF) is secreted onto LC, increasing LC output and norepinephrine concentration in the brain, which is thought to promote anxiety-like behavior. LC is also innervated by several structures that synthesize and release the endogenous opioid peptide enkephalin onto LC upon stressor termination. While the role of CRF neurotransmission within LC in mediating anxiety-like behavior and the behavioral response to stress has been well characterized, the role of enkephalinergic signaling at LC-expressed δ-opioid receptors has been comparatively understudied. We have previously shown that acute stressor exposure increases LC activity and anxiety-like behavior for at least one week. Here, we extend these findings by showing that these effects may be mediated at least in part through stress-induced downregulation of DORs within LC. Furthermore, overexpression of DORs in LC blocks the effects of stress on both LC firing properties and anxiety-like behavior. In addition, intra-LC infusions of enkephalin blocked stress-induced freezing behavior and promoted conditioned place preference. These findings indicate that enkephalinergic neurotransmission at DORs within LC is an important component of the behavioral response to stress and may drive reward-related behavior as well.
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spelling pubmed-93201952022-07-27 Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience Tkaczynski, John A. Borodovitsyna, Olga Chandler, Daniel J. Brain Sci Article The noradrenergic nucleus locus coeruleus is a key component of the stress circuitry of the brain. During stress, the neuropeptide corticotropin-releasing factor (CRF) is secreted onto LC, increasing LC output and norepinephrine concentration in the brain, which is thought to promote anxiety-like behavior. LC is also innervated by several structures that synthesize and release the endogenous opioid peptide enkephalin onto LC upon stressor termination. While the role of CRF neurotransmission within LC in mediating anxiety-like behavior and the behavioral response to stress has been well characterized, the role of enkephalinergic signaling at LC-expressed δ-opioid receptors has been comparatively understudied. We have previously shown that acute stressor exposure increases LC activity and anxiety-like behavior for at least one week. Here, we extend these findings by showing that these effects may be mediated at least in part through stress-induced downregulation of DORs within LC. Furthermore, overexpression of DORs in LC blocks the effects of stress on both LC firing properties and anxiety-like behavior. In addition, intra-LC infusions of enkephalin blocked stress-induced freezing behavior and promoted conditioned place preference. These findings indicate that enkephalinergic neurotransmission at DORs within LC is an important component of the behavioral response to stress and may drive reward-related behavior as well. MDPI 2022-06-29 /pmc/articles/PMC9320195/ /pubmed/35884666 http://dx.doi.org/10.3390/brainsci12070860 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tkaczynski, John A.
Borodovitsyna, Olga
Chandler, Daniel J.
Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title_full Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title_fullStr Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title_full_unstemmed Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title_short Delta Opioid Receptors and Enkephalinergic Signaling within Locus Coeruleus Promote Stress Resilience
title_sort delta opioid receptors and enkephalinergic signaling within locus coeruleus promote stress resilience
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320195/
https://www.ncbi.nlm.nih.gov/pubmed/35884666
http://dx.doi.org/10.3390/brainsci12070860
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