Targeting presynaptic H3 heteroreceptor in nucleus accumbens to improve anxiety and obsessive-compulsive-like behaviors
| Autor: | Shi-Yu Peng, Shu-Tao Xie, Jing-Ning Zhu, Jian-Jun Wang, Tian-Yu Ma, Qi-Peng Zhang, Bin Li, Xiao-Yang Zhang, Qian-Xiao Li, Li-Ping Shen, Qian-Xing Zhuang, Ming-Run Shi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Obsessive-Compulsive Disorder Patch-Clamp Techniques nucleus accumbens Synaptic Transmission Stereotaxic Techniques 0302 clinical medicine histamine H3 receptor Glutamates Medicine Neurons Multidisciplinary Biological Sciences anxiety Anxiety Disorders medicine.anatomical_structure Anxiety Histamine H3 receptor medicine.symptom Rats Transgenic Histamine Histamine H3 Antagonists medicine.drug_class Presynaptic Terminals Prefrontal Cortex Nucleus accumbens Heteroreceptor Anxiolytic Histamine Agonists 03 medical and health sciences Glutamatergic prelimbic prefrontal cortex Animals Humans Receptors Histamine H3 Afferent Pathways OCD business.industry Histaminergic Rats Optogenetics Disease Models Animal 030104 developmental biology Hypothalamic Area Lateral business Neuroscience 030217 neurology & neurosurgery Stress Psychological Basolateral amygdala |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance Anxiety disorders and obsessive-compulsive disorder (OCD) are highly prevalent and debilitating psychiatric disorders commonly co-occurring in our stressful modern life. Yet the common effective therapeutic target is still unknown. Here we report that activation of the histaminergic afferent system, particularly the histamine H3 receptor, in the nucleus accumbens (NAc) core, a vital node in the limbic loop, inhibits glutamatergic synaptic transmission in the circuit from the prelimbic prefrontal cortex (PrL) to NAc and improves both anxiety- and obsessive-compulsive-like behaviors induced by restraint stress. Our results define a common glutamatergic PrL–NAc circuit involved in both anxiety- and obsessive-compulsive-like behaviors modulated by the H3 presynaptic heteroreceptor and pave a path for developing potential strategies for clinical treatment of anxiety and OCD. 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. |
| Databáze: | OpenAIRE |
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