ArticleThe Journal of clinical investigation2020
Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Exploring the efficacy of cholinergic agents for the treatment of psychostimulant use disorder: a systematic review.Psychopharmacology · 2024Pooled it
- A neurodevelopmental model of eating disorder risk in midlife to older adulthood.Neuroscience and biobehavioral reviews · 2026Review
- Acetylcholine in Brain-Body Communication: Biological Mechanisms and Physiological Roles.International journal of molecular sciences · 2026Review
- Mapping the path to recovery: the intersection of cortical thickness reductions and serotonin transporter expression in anorexia nervosa.Molecular psychiatry · 2026Article
- Approved and Pipeline Pharmacological Interventions for Eating Disorders (2010-2025): 15 Years of Progress (or Lack Thereof).CNS drugs · 2026Review
- Avoidance habit learning in adolescents and young women with anorexia nervosa: an fMRI study.Journal of child psychology and psychiatry, and allied disciplines · 2026Article
- Toward a Genetic Signature of Resistance to Activity-Based Anorexia in Striatal Projecting Cortical Neurons.The International journal of eating disorders · 2025Article
- Integrating optical neuroscience tools into touchscreen operant systems.Nature protocols · 2025Review
- Genetics of Anorexia Nervosa: Translation to Future Personalized Therapies.The Psychiatric clinics of North America · 2025Review
- Exploring Habits in Anorexia Nervosa: Promise, Pitfalls, and Progress.Current psychiatry reports · 2025Review
- Nucleus accumbens deep brain stimulation in adult patients suffering from severe and enduring anorexia nervosa (STIMARS): protocol for a pilot study.Frontiers in psychiatry · 2025Article
- Cross-species translational paradigms for assessing positive valence system as defined by the RDoC matrix.Journal of neurochemistry · 2025Review
- Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders.Cell reports · 2024Article
- The Aggregation ofBiomedicines · 2024Article
- The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice.Nature communications · 2024Article
- A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa.The International journal of eating disorders · 2024Review
- Article
- Distinct cholinergic circuits underlie discrete effects of reward on attention.Frontiers in molecular neuroscience · 2024Review
- What influences food choices in anorexia nervosa? Disentangling cognitive and emotional components of decision-making by translational research.Neuroscience applied · 2024Review
- The multisensory mind: a systematic review of multisensory integration processing in Anorexia and Bulimia Nervosa.Journal of eating disorders · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 7 institutions in 4 countries.
Funding
Abstract
Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset of patients suffering from restrictive anorexia nervosa have enhanced habit formation compared with healthy controls. Habit formation is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glutamate cotransmission to regulate striatal functions. Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), we investigated the roles that acetylcholine and glutamate released by cholinergic interneurons play in habit formation and maladaptive eating. Silencing glutamate favored goal-directed behaviors and had no impact on eating behavior. In contrast, VAChTcKO mice were more prone to habits and maladaptive eating. Specific deletion of VAChT in the dorsomedial striatum of adult mice was sufficient to phenocopy maladaptive eating behaviors of VAChTcKO mice. Interestingly, VAChTcKO mice had reduced dopamine release in the dorsomedial striatum but not in the dorsolateral striatum. The dysfunctional eating behavior of VAChTcKO mice was alleviated by donepezil and by l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals that loss of acetylcholine leads to a dopamine imbalance in striatal compartments, thereby promoting habits and vulnerability to maladaptive eating in mice.
Indexed as
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.