ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Periaqueductal Gray Glutamatergic Transmission Governs Chronic Stress-Induced Depression.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- A Systematic Review of Direct Outputs from the Cerebellum to the Brainstem and Diencephalon in Mammals.Cerebellum (London, England) · 2024Pooled it
- A glutamatergic ventrolateral periaqueductal gray-lateral habenula pathway is associated with depression-like behavioral measures in young adult male mice with trigeminal neuropathic pain.The journal of headache and pain · 2026Article
- Lateral habenula and periaqueductal gray neurons signal reward prediction error and continuity of reward expectancy to drive reward-seeking behavior.Cell reports · 2026Article
- Chronic stress increases the susceptibility to chronic vulvar pain following acute vulvar inflammation in a preclinical model of vulvodynia.Molecular brain · 2026Article
- Inverted "u-shaped" association of cold-water immersion frequency with mental health and upper respiratory tract infection: a cross-sectional study.Brain, behavior, & immunity - health · 2025Article
- Subcortical modulation of the salience network during negative emotional processing in mood and anxiety disorders.Molecular psychiatry · 2025Article
- Chronic adolescent stress attenuates morphine-induced antinociception and central amygdala neuronal activation in adult Wistar rats.Physiology & behavior · 2025Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- The Locus Coeruleus-Periaqueductal Gray GABAergic Projection Regulates Comorbid Pain and Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Altered Microglial Plasticity in the Periaqueductal Grey of Pre-Symptomatic Mecp2-Heterozygous Mice Following Early-Life Stress.Neuromolecular medicine · 2025Article
- Periaqueductal gray passes over disappointment and signals continuity of remaining reward expectancy.Research square · 2025Article
- Periaqueductal gray passes over disappointment and signals continuity of remaining reward expectancy.bioRxiv : the preprint server for biology · 2024Article
- Article
- Impaired Ventrolateral Periaqueductal Gray-Ventral Tegmental area Pathway Contributes to Chronic Pain-Induced Depression-Like Behavior in Mice.Molecular neurobiology · 2023Article
- BTRX-246040 Acts Through the Ventrolateral Periaqueductal Gray to Exert Antidepressant-Relevant Actions in Mice.The international journal of neuropsychopharmacology · 2023Article
- Defensive and Emotional Behavior Modulation by Serotonin in the Periaqueductal Gray.Cellular and molecular neurobiology · 2023Review
- Neurocircuitry underlying the antidepressant effect of retrograde facial botulinum toxin in mice.Cell & bioscience · 2023Article
- Rapid antidepressant-like effects of muscarinic receptor antagonists require BDNF-dependent signaling in the ventrolateral periaqueductal gray.Psychopharmacology · 2022Article
- Neurobiology of Depression: Chronic Stress Alters the Glutamatergic System in the Brain-Focusing on AMPA Receptor.Biomedicines · 2022Review
- The interrelationship of chronic cough and depression: a prospective population-based study.ERJ open research · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying chronic stress-induced dysfunction of glutamatergic transmission that contribute to helplessness-associated depressive disorder are unknown. We investigated the relationship of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and stress, and the neuroplastic changes of stress-induced depression-like behavior in the ventrolateral periaqueductal gray (vlPAG). We conducted whole-cell patch-clamp electrophysiological recordings in the vlPAG neurons. Depression-like behavior was assayed using tail suspension test and sucrose preference test. Surface and cytosolic glutamate receptor 1 (GluR1) AMPA receptor expression was analyzed using western blotting. Phosphorylated GluR1 expression was quantified using western blotting and immunohistochemical analysis. Unpredictable inescapable foot shock stress caused reduction in glutamatergic transmission originating from both presynaptic and postsynaptic loci in the vlPAG that was associated with behavioral despair and anhedonia in chronic stress-induced depression. Pharmacological inhibition of GluR1 function in the vlPAG caused depression-like behavior. Diminished glutamatergic transmission was due to reduced glutamate release presynaptically and enhanced GluR1-endocytosis from the cell surface postsynaptically. Chronic stress-induced neuroplastic changes and maladaptive behavior were reversed and mimicked by administration of glucocorticoid receptor (GR) antagonist and agonist, respectively. However, chronic stress did not affect γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission in the vlPAG. These results demonstrate that depression-like behavior is associated with remarkable reduction in glutamatergic, but not GABAergic, transmission in the vlPAG. These neuroplastic changes and maladaptive behavior are attributed to GR-dependent mechanisms. As reduced GluR1-associated responses in the vlPAG contribute to chronic stress-induced neuroplastic changes, this cellular mechanism may be a critical component in the pathogenesis of stress-associated neuropsychiatric disorders.
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