A Comprehensive Voltammetric Characterization of In Vivo Histamine Dynamics Reveals Critical Modulatory Roles of This Elusive Messenger
Year: 2022
Type: preprint
Abstract: Histamine is well known for mediating peripheral inflammation, however, histamine is found in high concentrations in the brain where amongst other roles, this amine is a neuromodulator. Histamine modulation is critical for brain function, yet dynamic histamine chemistry is very difficult to measure and thus several fundamental aspects of the mechanisms that control the extracellular and modulatory behavior of this messenger remain undefined. In this work we undertake an in-depth characterization of in vivo histamine dynamics using fast-scan cyclic voltammetry at carbon fiber microelectrodes. We measure electrically evoked histamine in the mouse hypothalamus and find that histamine release is sensitive to pharmacological manipulation of synthesis, packaging, autoreceptor control of release, and metabolism. We find two breakthrough aspects of histamine modulation. First, there are differences in H3 receptor regulation of histamine between sexes showing that histamine release in female mice is more much tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, we find that a high dose of a commonly available antihistamine, the H1 receptor antagonist diphenhydramine, rapidly decreased serotonin levels. This high dose is considered overdose; however, this finding highlights the sheer significance of better consideration of the modulatory nuances of histamine on serotonin when studying/designing histamine targeting pharmaceuticals. We, thus, present the first in depth in vivo characterization of fast histamine dynamics and presents two breakthrough regulatory aspects of this elusive modulator.
Source: Research Square
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4220826002