ArticleBiological psychiatry2014
Regulation of fear responses by striatal and extrastriatal adenosine A2A receptors in forebrain.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
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- Genetic deletion of adenosine AGeroScience · 2026Article
- Exploring the Impact and Mechanisms of Coffee and Its Active Ingredients on Depression, Anxiety, and Sleep Disorders.Nutrients · 2025Review
- 40 Hz light flickering facilitates the glymphatic flow via adenosine signaling in mice.Cell discovery · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- Retrograde adenosine/ACell reports · 2024Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Adenosine AFrontiers in pharmacology · 2024Article
- Adenosine ATranslational psychiatry · 2023Article
- Molecular and Structural Insight into Adenosine AMolecular neurobiology · 2023Review
- Adenosine ABiomolecules · 2023Article
- Adenosine ABiomolecules · 2023Article
- Striatopallidal adenosine ANeuropharmacology · 2023Review
- CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine AInternational journal of molecular sciences · 2022Article
- Adenosine AMolecular neurobiology · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Adenosine Receptors in Neuropsychiatric Disorders: Fine Regulators of Neurotransmission and Potential Therapeutic Targets.International journal of molecular sciences · 2022Review
- Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundAdenosine A2A receptors (A2ARs) are enriched in the striatum but are also present at lower levels in the extrastriatal forebrain (i.e., hippocampus, cortex), integrating dopamine, glutamate, and brain-derived neurotrophic factor (BDNF) signaling, and are thus essential for striatal neuroplasticity and fear and anxiety behavior.
methodsWe tested two brain region-specific A2AR knockout lines with A2ARs selectively deleted either in the striatum (st-A2AR KO) or the entire forebrain (striatum, hippocampus, and cortex [fb-A2AR KO]) on fear and anxiety-related responses. We also examined the effect of hippocampus-specific A2AR deletion by local injection of adeno-associated virus type 5 (AAV5)-Cre into floxed-A2AR knockout mice.
resultsSelectively deleting A2ARs in the striatum increased Pavlovian fear conditioning (both context and tone) in st-A2AR KO mice, but extending the deletion to the rest of the forebrain apparently spared context fear conditioning and attenuated tone fear conditioning in fb-A2AR KO mice. Moreover, focal deletion of hippocampal A2ARs by AAV5-Cre injection selectively attenuated context (but not tone) fear conditioning. Deletion of A2ARs in the entire forebrain in fb-A2AR KO mice also produced an anxiolytic phenotype in both the elevated plus maze and open field tests, and increased the startle response. These extrastriatal forebrain A2AR behavioral effects were associated with reduced BDNF levels in the fb-A2AR KO hippocampus.
conclusionsThis study provides evidence that inactivation of striatal A2ARs facilitates Pavlovian fear conditioning, while inactivation of extrastriatal A2ARs in the forebrain inhibits fear conditioning and also affects anxiety-related behavior.
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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.