Ventral tegmental area dopamine revisited: effects of acute and repeated stress
Open accessAbstract
Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression.
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Animal evidence indicates that exposure to mild stressors potentiates dopaminergic activity whilst severe chronic stressors are associated with dopaminergic blunting.
“Given animal evidence that exposure to mild stressors potentiate dopaminergic activity whilst severe chronic stressors is associated with dopaminergic blunting (Holly and Miczek, 2016)”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
Long-lasting changes in dopamine function occur after single stress exposures, including altered responsivity to future stimulation, in a manner similar to that induced by drugs of abuse.
“Long-lasting changes in dopamine function occur after single stress exposures, including altered responsivity to future stimulation (Holly and Miczek, 2016) in a manner similar to that induced by drugs of abuse (Saal et al., 2003)”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
Different schedules, intensities, or modalities of stressor presentation can result in dramatically different behavioural and physiological responses.
“Other factors such as type of stressor may also cause different dopaminergic, autonomic and endocrine effects as work to date has demonstrated that different schedules, intensities, or modalities of stressor presentation can result in dramatically different behavioural and physiological responses (Holly and Miczek, 2016)”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
Exposure to repeated longer-term stressors leads to decreases in striatal dopamine function including nucleus accumbens dopamine output, reduced cocaine-induced nucleus accumbens dopamine release, and reduced striatal dopamine receptor availability.
“Exposure to repeated longer-term stressors leads to decreases in striatal dopamine function including nucleus accumbens dopamine output (Mangiavacchi et al., 2001), reduced cocaine-induced nucleus accumbens dopamine release (Shimamoto et al., 2011; Holly and Miczek, 2016), and reduced striatal dopamine receptor availability (Meaney et al., 2002; Brake et al., 2004).”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
The discrepant findings are likely to reflect differences in the stress paradigm employed, as mild stressors tend to potentiate dopamine function and severe/chronic stressors tend to reduce activity.
“These discrepant findings are likely to reflect differences in the stress paradigm employed as mild stressors tend to potentiate dopamine function and severe/chronic stressors tend to reduce activity (Holly and Miczek, 2016)”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
In chronic stress-induced depression, the blunting occurs primarily in the neurons projecting to the ventromedial striatum, where reward-related variables are processed.
“whereas in chronic stress-induced depression (Holly and Miczek, 2016), the blunting occurs primarily in the neurons projecting to the ventromedial striatum (Moreines et al., 2017), where reward-related variables are processed.”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
The response to later stressors of a different nature is generally cross-sensitized.
“the response to later stressors of a different nature is generally cross-sensitized”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
More severe or chronic uncontrollable stressors appear to reduce basal VTA dopamine activity.
“more severe or chronic uncontrollable stressors appear to reduce basal VTA dopamine activity”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
Mild or intermittent stressors appear to potentiate basal VTA dopamine neuron activity.
“mild or intermittent stressors appear to potentiate basal VTA dopamine neuron activity”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Holly and Miczek, 2016
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References 191 · Cited by 265
Research works printed but not linked: 2
- Selye H A syndrome produced by diverse nocuous agents. Nature 1936 138 32 32 9722327
- Tanimoto H Heisenberg M Gerber B Experimental psychology: event timing turns punishment to reward. Nature 2004 430 983 15329711
- Authors
- Holly, E. N., & Miczek, K. A.
- Affiliations
- Tufts University (US)
- Corresponding author
- Holly, Elizabeth N.
- Venue
- Psychopharmacology
- Published
- 2015-12-17
- Volume
- 233
- Issue
- 2
- Pages
- 163-186
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC4703498
- OpenAlex
- W2211535413
- Cited by
- 265
- References
- 191
- Citations by year
- 2026: 20 · 2025: 21 · 2024: 23 · 2023: 20 · 2022: 38 · 2021: 26 · 2020: 22 · 2019: 30 · 2018: 34 · 2017: 16 · 2016: 14 · 2013: 1
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institute on Drug Abuse (DA031734)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ventral tegmental area, dopaminergic neurons, acute stress, repeated stress, aversive stimuli, reward, medial prefrontal cortex, nucleus accumbens, addiction, depression, stress-related psychiatric disorders
- MeSH terms
- Animals, Dopamine, Humans, Stress, Psychological, Ventral Tegmental Area, Dopaminergic Neurons
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