ArticleTranslational psychiatry2024
Glutamate concentration of medial prefrontal cortex is inversely associated with addictive behaviors: a translational study.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neuroplasticity and recovery of the brain affected by substance use disorder: multilevel mechanisms and new therapeutic strategies (2020-2025).Frontiers in molecular neuroscience · 2026Pooled it
- Activation of mGlu2 Receptors Rescues Persistent Post-Methamphetamine Deficit in Object-in-Place Recognition Memory.Brain sciences · 2026Article
- Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness.bioRxiv : the preprint server for biology · 2026Article
- Sex and dose-dependent effects of cannabidiol on cocaine consumption in mice.Translational psychiatry · 2026Article
- Medial prefrontal cortex circuit dynamics involved in stage-specific addiction.Brain structure & function · 2025Review
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Authors and funding
10 authors.
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Abstract
In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.
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