ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces both Anxiety and Depressive-Like Symptoms.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 91 citations in OpenAlex.
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- Glutamatergic dysfunction of astrocytes in paraventricular nucleus of thalamus contributes to adult anxiety susceptibility in adolescent ethanol exposed mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- CeA-projecting VTA neurons contribute to alcohol withdrawal-induced anxiety-like behavior in male and female rats.Alcohol (Fayetteville, N.Y.) · 2026Article
- An Overview of Depression Pathogenesis: Prevailing Hypotheses and Associated Neurobiological Underpinnings Primarily Evidenced by Rodent Studies.Depression and anxiety · 2026Review
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Deficit of neuronal EAAT2 impairs hippocampus CA3 neuron's activity and may induce depressive like behaviors.Journal of advanced research · 2026Article
- Astrocyte Ezrin defines resilience to stress-induced depressive behaviours in mice.National science review · 2026Article
- Dapagliflozin Reverses LPS-Induced Depressive-Like Behavior in Mice via Modulation of Glutamate and NF-κB.Genes, brain, and behavior · 2025Article
- Astrocytes in Rodent Anxiety-Related Behavior: Role of Calcium and Beyond.International journal of molecular sciences · 2025Review
- Enhancement of Glutamate Uptake as Novel Antiseizure Approach: Preclinical Proof of Concept.Annals of neurology · 2025Article
- Astrocytes in the Ventral Hippocampus Bidirectionally Regulate Innate and Stress-Induced Anxiety-Like Behaviors in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Arc and BDNF mediated effects of hippocampal astrocytic glutamate uptake blockade on spatial memory stages.Communications biology · 2024Article
- The role of glutamate and glutamine metabolism and related transporters in nerve cells.CNS neuroscience & therapeutics · 2024Review
- Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde.Sleep medicine: X · 2023Article
- Astrocytes in human central nervous system diseases: a frontier for new therapies.Signal transduction and targeted therapy · 2023Review
- Exploring the bidirectional relationship between pain and mental disorders: a comprehensive Mendelian randomization study.The journal of headache and pain · 2023Article
- Electroacupuncture prevents astrocyte atrophy to alleviate depression.Cell death & disease · 2023Article
- Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression.Science advances · 2022Article
- High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.Molecular psychiatry · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Depression has been associated with abnormalities in glutamatergic neurotransmission and decreased astrocyte number in limbic areas. We previously demonstrated that global and prefrontal cortical blockade of the astrocytic glutamate transporter (GLT-1) induces anhedonia and c-Fos expression in areas that regulate anxiety, including the central amygdala (CEA). Given the role of the amygdala in anxiety and the high degree of comorbidity between anxiety and depression, we hypothesized that GLT-1 blockade in the CEA would induce symptoms of anhedonia and anxiety in rats. We microinjected the GLT-1 inhibitor, dihydrokainic acid (DHK), into the CEA and examined effects on intracranial self-stimulation (ICSS) as an index of hedonic state, and on behavior in two anxiety paradigms, elevated plus maze (EPM) and fear conditioning. At lower doses, intra-CEA DHK produced modest increases in ICSS responding (T0). Higher doses resulted in complete cessation of responding for 15 min, suggesting an anhedonic or depressive-like effect. Intra-CEA DHK also increased anxiety-like behavior such that percent time in the open arms and total entries were decreased in the EPM and acquisition of freezing behavior to the tone was increased in a fear-conditioning paradigm. These effects did not appear to be explained by non-specific changes in activity, because effects on fear conditioning were assessed in a drug-free state, and a separate activity test showed no significant effects of intra-CEA DHK on locomotion. Taken together, these studies suggest that blockade of GLT-1 in the CEA is sufficient to induce both anhedonia and anxiety and therefore that a lack of glutamate uptake resulting from glial deficits may contribute to the comorbidity of depression and anxiety.
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