Cited by 231Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam

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Bagley, J, Moghaddam, B·1997·Neuroscience

DOI 10.1016/s0306-4522(96)00435-6

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Abstract

Acute stress has been associated with activation of glutamate efflux in forebrain structures. The present study sought to characterize the extracellular dynamics of glutamate in response to acute and repeated stress in the prefrontal cortex and hippocampus in rats. One-minute sampling of extracellular glutamate levels was performed during repeated tail-pinch stress. Animals were stressed three times, beginning at approximately 10.30 a.m. and continuing at 2.5-h intervals. In the prefrontal cortex, the initial 10-min tail pinch produced a robust increase in extracellular levels of glutamate. This increase was apparent immediately (i.e. 1 min) after the start of the stress procedure. The second tail pinch produced a smaller increase in glutamate levels while the third tail pinch did not significantly increase these levels. In the hippocampus, the initial stress response was smaller in magnitude than that observed in the prefrontal cortex. Furthermore, responses to subsequent tail pinches were similar to that seen following the first tail pinch. Treatment with diazepam (3 mg/kg/i.p.) 30 min before the first stress session abolished the stress response in the prefrontal cortex and hippocampus. However, in the prefrontal cortex, the second tail pinch (performed approximately 3 h after diazepam administration) produced a robust increase in glutamate efflux. In contrast, in the hippocampus of diazepam-treated rats, the second tail pinch produced a small delayed response. Pretreatment with saline resulted in non-significant responses to all three tail pinches in the prefrontal cortex. The present study suggests that: (i) stress produces a rapid increase in glutamate efflux in the prefrontal cortex and hippocampus, (ii) repeated stress reveals tolerance in the glutamatergic response in the prefrontal cortex, (iii) saline and diazepam pretreatment reduce the stress-induced efflux of glutamate in the prefrontal cortex, and (iv) exposure to diazepam may prevent the prefrontal cortex from adapting its response to the subsequent stressor. These finding are consistent with the role of the prefrontal cortex as a region which may regulate reactions to aversive stimuli.

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Authors: Bagley, J., & Moghaddam, B.
Affiliations: Yale University (US)
Corresponding author: Moghaddam, B
ORCID: Moghaddam, B
Venue: Neuroscience
Publisher: Elsevier BV
Published: 1997-01
Volume: 77
Issue: 1
Pages: 65-73
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/s0306-4522(96)00435-6
OpenAlex: W2003983445
Cited by: 231
References: 45
Citations by year: 2026: 2 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 13 · 2016: 7 · 2015: 11 · 2014: 16 · 2013: 12 · 2012: 17
FWCI: 3.22
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 407 d)
Locations: Neuroscience (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (44866)
National Institute of Mental Health (MH 44866, MH48404, P50MH044866)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: glutamate efflux, repeated stress, prefrontal cortex, hippocampus, diazepam, stress tolerance, stress adaptation, aversive stimuli
MeSH terms: Animals, Diazepam, Hippocampus, Male, Sodium Chloride, Stress, Physiological, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Microdialysis, Glutamic Acid, GABA Modulators, Rats

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Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam

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