Histaminergic modulation of acetylcholine-induced γ oscillations in rat hippocampus

We investigated the interaction between ambient histamine and acetylcholine by studying γ oscillations in rat hippocampus, induced by bath application of acetylcholine (10 µM combined with 2 µM physostigmine). The power of γ was significantly increased by the H1 antagonist, fexofenadine, and H2 receptor agonist, dimaprit, and reduced by the H2 receptor antagonist, cimetidine. These effects suggest an interference with ambient histamine. Depletion of histamine from their fibers by hypoxia and blockade of histamine uptake resulted in loss of the fexofenadine-mediated and cimetidine-mediated effects on acetylcholine-induced γ. We conclude that acetylcholine can cause histamine release from histaminergic fibers and thereby can influence attentional states by augmenting γ. This effect is likely due to activation of H2 receptors by histamine and thereby might contribute to the previously described enhancement of working memory.