Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala
Abstract
A number of experimental results has pointed to a cholinergic involvement in the stress response. Recently, analytical techniques have become available to measure acetylcholine release in vivo during exposure to various stressors. In these experiments, microdialysis was used to monitor acetylcholine output every 15 min in the dorsal hippocampus, amygdala, nucleus accumbens and prefrontal cortex before, during and after 1 h of restraint, including a 15-min session of intermittent tail-shock (1/min, 1 mA, 1-s duration) in rats. In response to the stressful event, acetylcholine release was significantly increased in the prefrontal cortex (186%; p < 0.01) and hippocampus (168%; P < 0.01) but not in the amygdala or nucleus accumbens. The sole effects observed in the amygdala and nucleus accumbens occurred upon release from the restrainer, at which point acetylcholine levels were significantly elevated in both areas (amygdala: 150%; P < 0.05; nucleus accumbens: 13%; P < 0.05). An enhanced acetylcholine release was also evident during this sample period in the hippocampus and prefrontal cortex. These data demonstrate an enhancement of cholinergic activity in response to stress in two acetylcholine projection systems (hippocampus and prefrontal cortex) but not in the intrinsic acetylcholine system of the nucleus accumbens or the extrinsic innervation of the amygdala. Moreover, the data showed that relief from stress was accompanied by a more ubiquitous acetylcholine response that extended to each site tested.
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There is evidence that extracellular levels of acetylcholine fluctuate in a manner that is not consistent with localized clearance of a synaptic transmitter.
“There is also evidence that extracellular levels of ACh fluctuate in a manner that is not consistent with localized clearance of a synaptic transmitter (Hajnal et al., 1998; Laplante et al., 2004; Mark et al., 1996; Parikh et al., 2004; Reid et al., 1998).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Mark et al., 1996
Stress increases ACh release in a brain region-specific manner.
“Several studies have shown that stress increases ACh release in a brain region-specific manner (Mark et al., 1996).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Mark et al., 1996
Hippocampal and cortical ACh levels can increase following restraint stress in rats, while ACh levels in the amygdala are unchanged.
“For instance, hippocampal and cortical ACh levels can increase following restraint stress in rats, while ACh levels in the amygdala are unchanged”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Mark et al., 1996
Relief from stress leads to an increase in cholinergic signaling in the amygdala and PFC.
“Interestingly, relief from stress leads to an increase in cholinergic signaling in the amygdala and PFC (Mark et al., 1996)”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Mark et al., 1996
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- Authors
- Mark, G. P., Rada, P. V., & Shors, T. J.
- Affiliations
- Princeton University (US)
- Corresponding author
- Mark, G.P
- ORCID
- Shors, T.J
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 74
- Issue
- 3
- Pages
- 767-774
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2014948578
- Cited by
- 149
- References
- 64
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 2 · 2016: 1 · 2015: 9 · 2014: 2 · 2013: 4 · 2012: 7
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- acetylcholine release, stress response, cholinergic system, hippocampus, prefrontal cortex, amygdala, nucleus accumbens, restraint stress, microdialysis, stress reduction
- MeSH terms
- Acetylcholine, Amygdala, Animals, Brain, Extracellular Space, Hippocampus, Male, Nucleus Accumbens, Organ Specificity, Restraint, Physical, Stress, Psychological, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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