ArticleProceedings of the National Academy of Sciences of the United States of America2020
Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 82 citations in OpenAlex.
- Advances in Neurotransmission: The Remarkable Versatility of the Nervous System.International journal of molecular sciences · 2026Article
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- Histamine shapes the neurocomputational dynamics of human learning.Nature communications · 2026Article
- Change in brain molecular landscapes following electrical stimulation of the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Reciprocal regulation of the HbioRxiv : the preprint server for biology · 2025Article
- Targeting Histamine H4 Receptor in the Rostral Ventromedial Medulla to Relieve Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A whole-brain male mouse atlas of long-range inputs to histaminergic neurons.Nature communications · 2025Article
- Oxytocin Improves Autistic Behaviors by Positively Shifting GABA Reversal Potential via NKCC1 in Early-Postnatal-Stage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- GHS-R1a signaling drives anxiety-related behavior by shaping excitability of ventromedial hypothalamic neurons.Nature communications · 2025Article
- Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson's Disease.Neuroscience bulletin · 2025Article
- Mechanisms of nucleus accumbens deep brain stimulation in treating mental disorders.Fundamental research · 2025Review
- Projections from subfornical organ to bed nucleus of the stria terminalis modulate inflammation-induced anxiety-like behaviors in mice.Science advances · 2024Article
- Article
- Histaminergic System Activity in the Central Nervous System: The Role in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice.Molecular psychiatry · 2024Article
- Nucleus accumbens ghrelin signaling controls anxiety-like behavioral response to acute stress.Behavioral and brain functions : BBF · 2024Article
- Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice.Scientific reports · 2024Article
- Targeting Histamine and Histamine Receptors for Memory Regulation: An Emotional Perspective.Current neuropharmacology · 2024Review
- The Diverse Network of Brain Histamine in Feeding: Dissect its Functions in a Circuit-Specific Way.Current neuropharmacology · 2024Review
- Oxytocin Receptor in Cerebellar Purkinje Cells Does Not Engage in Autism-Related Behaviors.Cerebellum (London, England) · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL- and not BLA- and vHipp-NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL-NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.
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