ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
Astrocytes determine conditioned response to morphine via glucocorticoid receptor-dependent regulation of lactate release.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Multisystem regulation of reward and addiction: beyond the dopaminergic system.Frontiers in pharmacology · 2026Review
- Alcohol dependence-induced astrocyte immune activation in the nucleus accumbens.Neurobiology of disease · 2025Article
- Preventive effects of crocin and meloxicam on morphine withdrawal symptoms in mice: behavioral and biochemical insights.BMC pharmacology & toxicology · 2025Article
- Alcohol Dependence-Induced Astrocyte Immune Activation in the Nucleus Accumbens.bioRxiv : the preprint server for biology · 2025Article
- Astrocytes and Astrocyte-Derived Extracellular Conduits in Opiate-Mediated Neurological Disorders.Cells · 2025Review
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
- Altered neuronal lactate dehydrogenase A expression affects cognition in a sex- and age-dependent manner.iScience · 2024Article
- Astrocytic transcriptional and epigenetic mechanisms of drug addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawal.Science advances · 2023Article
- Role of stress-related glucocorticoid changes in astrocyte-oligodendrocyte interactions that regulate myelin production and maintenance.Histology and histopathology · 2023Review
- Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression.Science advances · 2022Article
- Glucocorticoid-Regulated Kinase CAMKIγ in the Central Amygdala Controls Anxiety-like Behavior in Mice.International journal of molecular sciences · 2022Article
- Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice.Cellular and molecular neurobiology · 2022Article
- Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake.Translational psychiatry · 2022Article
- Astrocytes: the neglected stars in the central nervous system and drug addiction.Medical review (2021) · 2022Review
- Astrocyte Molecular Clock Function in the Nucleus Accumbens Is Important for Reward-Related Behavior.Biological psychiatry · 2022Article
- Knockdown of Astrocytic Monocarboxylate Transporter 4 in the Motor Cortex Leads to Loss of Dendritic Spines and a Deficit in Motor Learning.Molecular neurobiology · 2022Article
- Looking to the stars for answers: Strategies for determining how astrocytes influence neuronal activity.Computational and structural biotechnology journal · 2022Review
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, neurons have been the primary focus of research on the role of glucocorticoids in the regulation of brain function and pathological behaviors, such as addiction. Astrocytes, which are also glucocorticoid-responsive, have been recently implicated in the development of drug abuse, albeit through as yet undefined mechanisms. Here, using a spectrum of tools (whole-transcriptome profiling, viral-mediated RNA interference in vitro and in vivo, behavioral pharmacology and electrophysiology), we demonstrate that astrocytes in the nucleus accumbens (NAc) are an important locus of glucocorticoid receptor (GR)-dependent transcriptional changes that regulate rewarding effects of morphine. Specifically, we show that targeted knockdown of the GR in the NAc astrocytes enhanced conditioned responses to morphine, with a concomitant inhibition of morphine-induced neuronal excitability and plasticity. Interestingly, GR knockdown did not influence sensitivity to cocaine. Further analyses revealed GR-dependent regulation of astroglial metabolism. Notably, GR knockdown inhibited induced by glucocorticoids lactate release in astrocytes. Finally, lactate administration outbalanced conditioned responses to morphine in astroglial GR knockdown mice. These findings demonstrate a role of GR-dependent regulation of astrocytic metabolism in the NAc and a key role of GR-expressing astrocytes in opioid reward processing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.