ArticleScience advances2022
A red nucleus-VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Effects of exercise of different intensities on withdrawal symptoms among people with substance use disorder: a systematic review and meta-analysis.Frontiers in physiology · 2023Pooled it
- Endurance exercise relieves methamphetamine craving behaviors via hepatic synthesis of N-Acetylneuraminic acid.Molecular psychiatry · 2026Article
- Nucleus Accumbens D1 Receptor Neurons Contribute to Emotional and Metabolic Adaptation to Chronic Hypoxia.Neuroscience bulletin · 2026Article
- Social reward outcompetes drug seeking dopaminergic ensembles to prevent relapse.Nature communications · 2026Article
- Whole-Brain Neural Connectivity to Cholinergic Neurons in the Lower Thoracic Intermediolateral Column.CNS neuroscience & therapeutics · 2026Article
- Exercise as a multiscale recalibration of stress-related homeostatic balance.Frontiers in neuroscience · 2026Review
- Aerobic exercise for substance use disorders: therapeutic effects and underlying mechanisms.Frontiers in medicine · 2026Review
- Effects of aerobic exercise on approach-avoidance responses and prefrontal activity in individuals with tobacco dependence.Frontiers in sports and active living · 2026Article
- The impact of sex, species, environmental context, and alternative reinforcers in animal models of cocaine use disorders.Pharmacology, biochemistry, and behavior · 2025Review
- Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice.Biomedicines · 2025Article
- Physical exercise activates a PVN-NAc oxytocin circuit to relieve stress-induced depressive-like behaviors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Treadmill exercise training inhibits morphine CPP by reversing morphine effects on GABA neurotransmission in D2-MSNs of the accumbens-pallidal pathway in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Optical Intracranial Self-Stimulation (oICSS): A New Behavioral Model for Studying Drug Reward and Aversion in Rodents.International journal of molecular sciences · 2024Review
- The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.The international journal of neuropsychopharmacology · 2023Article
- Drug abuse results in metabolic and epigenetic changes in body which may contribute to disease risk: Role of L-carnitine and nutrients.Advances in drug and alcohol research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons. Optogenetic stimulation of this pathway was rewarding, as assessed by intracranial self-stimulation and conditioned place preference, whereas optical inhibition blocked wheel-running behavior. Running wheel access decreased cocaine self-administration and cocaine seeking during extinction. Last, optogenetic stimulation of the RNm-to-VTA glutamate pathway inhibited responding to cocaine. Together, these findings indicate that physical exercise activates a specific RNm-to-VTA glutamatergic pathway, producing exercise reward and reducing cocaine intake.
Identifiers
What OpenQuestion holds
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.