Autoregulation of histamine release in medulla oblongata via H3-receptors in rabbits

The release of histamine (HA) from the rostral ventrolateral medulla (RVL), the raphe nuclei (nR), and the solitary nucleus (nTS) was investigated in anesthetized rabbits using microdialysis and high-performance liquid chromatography. HA release upon electrical stimulation of the posterior hypothalamus (PH), where histaminergic cell bodies are located, was increased to 168% of the baseline level in the RVL (n = 6), 139% of the baseline level in the nR (n = 5), and 166% of the baseline level in the nTS (n = 4). Upon perfusion of thioperamide, an H3-receptor antagonist, via a microdialysis probe, HA release from the RVL, nR and nTS increased. The increase in HA release from the RVL, nR and nTS following thioperamide perfusion was suppressed by co-perfusion of thioperamide and an H3-receptor agonist, imetit. We found that HA is released from the RVL, nR and nTS, that the HA release from all three areas is increased upon stimulation of the PH, and that the HA release is locally influenced in opposite directions by thioperamide and imetit. These results suggest that HA release in the medulla oblongata is controlled by the PH and that H3-receptors participate in the autoregulation of HA release by providing negative feedback locally. Autoregulation of HA release via H3-receptors may be important for maintaining tonic output to the sympathetic nervous system.