ArticleTranslational psychiatry2012
The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.
Article in Translational psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 4 citations in OpenAlex.
- Examination of the shared genetic basis of anorexia nervosa and obsessive-compulsive disorder.Molecular psychiatry · 2020Pooled it
- Animal Models for Anorexia Nervosa-A Systematic Review.Frontiers in human neuroscience · 2020Pooled it
- Neuropsychological and metabolic interconnectivity in obesity, anorexia and bulimia nervosa - an integrative literature review.Metabolic brain disease · 2026Review
- Activation of 5-HT4 receptors reverses stress-induced dopamine system dysregulation.Neuropharmacology · 2026Article
- Comprehensive insights into emerging advances in the Neurobiology of anorexia.Journal of advanced research · 2026Review
- Brain serotonin, oxytocin, and their interaction: Relevance for eating disorders.Journal of psychopharmacology (Oxford, England) · 2025Review
- Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine.Molecular and cellular neurosciences · 2023Article
- Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine.bioRxiv : the preprint server for biology · 2023Article
- The serotonergic system dysfunction in diabetes mellitus.Frontiers in cellular neuroscience · 2022Review
- 5-HTACS chemical neuroscience · 2021Article
- Review
- Serotonin receptor 4 in the hippocampus modulates mood and anxiety.Molecular psychiatry · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Developmental programming of appetite and growth in male rats increases hypothalamic serotonin (5-HT)5A receptor expression and sensitivity.International journal of obesity (2005) · 2020Article
- Genetic contributions to the etiology of anorexia nervosa: New perspectives in molecular diagnosis and treatment.Molecular genetics & genomic medicine · 2020Review
- Serotonin in Animal Cognition and Behavior.International journal of molecular sciences · 2020Review
- Serotonergic system, cognition, and BPSD in Alzheimer's disease.Neuroscience letters · 2019Review
- Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders.International journal of molecular sciences · 2018Review
- Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression.Biomolecules & therapeutics · 2018Review
- Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.Medicine and science in sports and exercise · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In mental diseases, the brain does not systematically adjust motor activity to feeding. Probably, the most outlined example is the association between hyperactivity and anorexia in Anorexia nervosa. The neural underpinnings of this 'paradox', however, are poorly elucidated. Although anorexia and hyperactivity prevail over self-preservation, both symptoms rarely exist independently, suggesting commonalities in neural pathways, most likely in the reward system. We previously discovered an addictive molecular facet of anorexia, involving production, in the nucleus accumbens (NAc), of the same transcripts stimulated in response to cocaine and amphetamine (CART) upon stimulation of the 5-HT(4) receptors (5-HTR(4)) or MDMA (ecstasy). Here, we tested whether this pathway predisposes not only to anorexia but also to hyperactivity. Following food restriction, mice are expected to overeat. However, selecting hyperactive and addiction-related animal models, we observed that mice lacking 5-HTR(1B) self-imposed food restriction after deprivation and still displayed anorexia and hyperactivity after ecstasy. Decryption of the mechanisms showed a gain-of-function of 5-HTR(4) in the absence of 5-HTR(1B), associated with CART surplus in the NAc and not in other brain areas. NAc-5-HTR(4) overexpression upregulated NAc-CART, provoked anorexia and hyperactivity. NAc-5-HTR(4) knockdown or blockade reduced ecstasy-induced hyperactivity. Finally, NAc-CART knockdown suppressed hyperactivity upon stimulation of the NAc-5-HTR(4). Additionally, inactivating NAc-5-HTR(4) suppressed ecstasy's preference, strengthening the rewarding facet of anorexia. In conclusion, the NAc-5-HTR(4)/CART pathway establishes a 'tight-junction' between anorexia and hyperactivity, suggesting the existence of a primary functional unit susceptible to limit overeating associated with resting following homeostasis rules.
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