Histaminergic transmission potentiates post-traumatic stress-induced expression of anxiety in mice.
Level 5 - mechanism / opinion, no new human data
Animal research (rodent model)
PubMed 40550464 · doi:10.1016/j.neuropharm.2025.110564
What was done
Mice were exposed to a single prolonged stress (SPS) protocol and rested for 7 days. On day 8, non-stressed and SPS-exposed mice received intracerebroventricular (i.c.v.) administration of various histaminergic modulators: histamine, l-histidine (precursor), FMPH (H1 agonist), amthamine (H2 agonist), cetirizine (0.1 μg/mouse, H1 antagonist), ranitidine (10 μg/mouse, H2 antagonist), or thioperamide (2 and 10 μg/mouse, H3 inverse agonist). Anxiety-like behavior was evaluated using the light-dark box (LDB) test, followed by measurement of corticosterone (CORT), CREB, and BDNF levels across the whole brain, prefrontal cortex (PFC), amygdala, and hippocampus, along with blood and brain histamine levels.
What was found
The abstract does not report exact numerical values or effect sizes. Reported directional findings include: - SPS increased anxiety-like behavior, elevated blood and brain histamine as well as CORT levels, and decreased BDNF and CREB expression across all tested brain regions. - Histaminergic enhancers (histamine, l-histidine, H1/H2 agonists) potentiated anxiety-like behavior, further elevated CORT, and further reduced BDNF/CREB levels. - Central injection of cetirizine (0.1 μg/mouse) or ranitidine (10 μg/mouse) completely reversed SPS-induced behavioral and biochemical changes. - Thioperamide (2 and 10 μg/mouse) restored basal anxiety behavior, CREB, and BDNF expression without altering elevated CORT levels.
Why it matters
The study demonstrates that central histamine receptor signaling contributes to trauma-induced anxiety-like behavior and neurochemical alterations in mice, identifying histaminergic pathways as potential mechanistic targets in stress-related anxiety research.
Limits
This is an animal study in mice; findings cannot be directly translated to human post-traumatic stress disorder. Total sample size and individual group sizes are not reported in the abstract. Quantitative data, error bars, and exact statistical effect sizes are omitted from the record. Compounds were administered directly into cerebral ventricles (i.c.v.), which does not reflect therapeutic administration routes in humans.
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