Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat
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Published:2023-07-07
Issue:13
Volume:24
Page:11193
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Winzenried Eric T.1ORCID, Everett Anna C.1ORCID, Saito Erin R.2ORCID, Miller Roxanne M.2ORCID, Johnson Taylor1ORCID, Neal Eliza2ORCID, Boyce Zachary1, Smith Calvin1, Jensen Chloe1, Kimball Spencer2, Brantley Adam2, Melendez Gabriel1, Moffat Devin2ORCID, Davis Erin2, Aponik Lyndsey1, Crofts Tyler2, Dabney Bryson2, Edwards Jeffrey G.12ORCID
Affiliation:
1. Neuroscience Center, Brigham Young University, Provo, UT 84602, USA 2. Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA
Abstract
Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing β-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.
Funder
National Institute of Drug Abuse National Institute of Neurological Disorders and Stroke
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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