NMDA Receptor Blockade Alters Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex
Open accessAbstract
The development and relapse of many psychopathologies can be linked to both stress and prefrontal cortex dysfunction. Glucocorticoid stress hormones target medial prefrontal cortex (mPFC) and either chronic stress or chronic administration of glucocorticoids produces dendritic remodeling in prefrontal pyramidal neurons. Exposure to stress also causes an increase in the release of the excitatory amino acid glutamate, which binds to N-methyl-D-aspartate (NMDA) receptors, which are plentiful in mPFC. NMDA receptor activation is crucial for producing hippocampal dendritic remodeling due to stress and for dendritic reorganization in frontal cortex after cholinergic deafferentation. Thus, NMDA receptors could mediate stress-induced dendritic retraction in mPFC. To test this hypothesis, dendritic morphology of pyramidal cells in mPFC was assessed after blocking NMDA receptors with the competitive NMDA antagonist ±3-(2-carboxypiperazin-4yl)propyl-1-phosphonic acid (CPP) during restraint stress. Administration of CPP prevented stress-induced dendritic atrophy. Instead, CPP-injected stressed rats showed hypertrophy of apical dendrites compared with controls. These results suggest that NMDA activation is crucial for stress-induced dendritic atrophy in mPFC. Furthermore, NMDA receptor blockade uncovers a new pattern of stress-induced dendritic changes, suggesting that other neurohormonal changes in concert with NMDA receptor activation underlie the net dendritic retraction seen after chronic stress.
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A stress-induced NMDA-dependent dendritic remodeling has been reported in medial prefrontal cortex neurons.
“A stress-induced NMDA-dependent dendritic remodeling has been reported in mPFC neurons.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [47]
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- Authors
- Martin, K. P., & Wellman, C. L.
- Affiliations
- Indiana University Bloomington (US)
- ORCID
- Wellman, C. L.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-07
- Volume
- 21
- Issue
- 10
- Pages
- 2366-2373
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC3697127
- OpenAlex
- W2165208650
- Cited by
- 138
- References
- 63
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 16 · 2020: 8 · 2019: 10 · 2018: 5 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 14 · 2013: 13 · 2012: 14
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R03MH087794)
- 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
- NMDA receptor blockade, dendritic remodeling, medial prefrontal cortex, chronic stress, restraint stress, dendritic atrophy, CPP, glucocorticoids, glutamate, pyramidal neurons, apical dendrites
- MeSH terms
- Animals, Dendrites, Male, Piperazines, Stress, Psychological, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Pyramidal Cells, Excitatory Amino Acid Antagonists, Rats
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