Using a histamine receptor antibody to understand mania in a mouse model.
In new research, published in Cell Reports, a group from Zhejiang University, China, have uncovered a missing piece which potentially underlies the enhanced activity of dopamine neurons in the ventral tegmental area (VTA) and manic-like behaviors. What’s surprising about this is the mediator: histamine (1). They found that following the deletion of histamine H2 receptors in these neurons, mice displayed hyperactivity and mood elevation – hallmarks of mania.
The research elaborates on the role histamine H2 receptor plays in controlling dopamine neuron activity through interactions with GABAergic inhibition. They point out how approximately 60% of dopamine neurons in the VTA expressed histamine H2 receptors, with higher expression compared to H1 receptors in these neurons. By reducing H2 receptors expression, via H2 receptors knockout mice (nicely demonstrated with Alomone Labs’ Anti-Histamine H2 Receptor (HRH2) (extracellular) Antibody (#AHR-002), Figure 1), the researchers saw decreased inhibitory signals, which allowed dopamine neurons to become overactive, and the mice to present elevated mood.
Figure 1. Decreased protein levels of H2R in VTADA-shHrh2 mice. Representative images (left) and quantification (right) of western blot of VTA samples in VTADA-GFP and VTADA-shHrh2 mice. GAPDH serves as loading control. n= 4 mice per lane. n= 3 times. Unpaired two tailed t test, **P < 0.01. error bars, SEM. Figure and legend from Ma et al. (1).
This study brings fresh insight into the role of histamine in dopamine regulation and mood disorders like bipolar disorder, and even offers a new target in the potential treatment of mania.
If you’re looking in histamine H2 receptors or other G-protein-coupled receptor (GPCRs), we have a range of reliable tools to make it easier to investigate these pathways.
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Reference
1. S. Ma, Q. Ma, S. Hu, X. Mo, C. Zhu, X. Zhang, Z. Jia, L. Tang, L. Jiang, Y. Cui, Z. Chen, W. Hu, X. Zhang, Deletion of histamine H2 receptor in VTA dopaminergic neurons of mice induces behavior reminiscent of mania. Cell Reports43, 114717 (2024). DOI: https://doi.org/10.1016/j.celrep.2024.114717.
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