ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Effects of Prior Cognitive Exertion on Physical Performance: A Systematic Review and Meta-analysis.Sports medicine (Auckland, N.Z.) · 2020Pooled it
- Adenosine APsychopharmacology · 2026Article
- Neurochemical drivers of effort: The roles of dopamine and beyond in physical and cognitive exertion.Neuroscience and biobehavioral reviews · 2026Review
- Modulation of hierarchical motor sequence learning by alpha-synuclein and the adenosine ANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Adenosine A2A receptors in the nucleus accumbens regulate stress resilience and predict susceptibility to stress-induced affective disturbances.Purinergic signalling · 2026Article
- A2A-Positive Neurons in the Nucleus Accumbens Core Regulate Effort Exertion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Inhibition of striatal indirect pathway during second postnatal week leads to long-lasting deficits in motivated behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Moving to a non-dopaminergic approach for the treatment of OFF fluctuations in Parkinson's disease.Clinical parkinsonism & related disorders · 2025Review
- Ventral Pallidum and Amygdala Cooperate to Restrain Reward Approach under Threat.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- The striatum drives the ergogenic effects of caffeine.Purinergic signalling · 2023Article
- Striatopallidal adenosine ANeuropharmacology · 2023Review
- The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks.Frontiers in cellular neuroscience · 2023Review
- The Arousal-motor Hypothesis of Dopamine Function: Evidence that Dopamine Facilitates Reward Seeking in Part by Maintaining Arousal.Neuroscience · 2022Article
- Brain structural and functional connectivity alterations are associated with fatigue in neuromyelitis optica spectrum disorder.BMC neurology · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Vigor, Effort-Related Aspects of Motivation and Anhedonia.Current topics in behavioral neurosciences · 2022Review
- International society of sports nutrition position stand: caffeine and exercise performance.Journal of the International Society of Sports Nutrition · 2021Review
- Inactivation of the Ventral Pallidum by GABANeurochemical research · 2020Article
- The belated US FDA approval of the adenosine APurinergic signalling · 2020Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A(2A) receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A(2A) receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A(2A) receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A(2A) receptors immunoreactivity. Moreover, activation of accumbens A(2A) receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABA(A) agonist muscimol into ventral pallidum (i.e., "disconnection" methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A(2A) receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression.
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Registered trials
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.