Cerebellar fastigial nucleus histamine and its H2 but not H1 receptors might inhibit acetic acid-induced visceral nociception and improve motor coordination in rats: role of opioid system

The cerebellum and its deep nuclei contribute to the regulation of important functions including motor coordination and pain. Histamine modulates some functions of the fastigial nucleus (FN) such as motor coordination. In this study, by application of histamine and activation of its H1 and H2 receptors, the FN processing of visceral pain, general locomotor activity and motor coordination were targeted. The possible mechanism of action was followed by the inhibition of opioid receptors. The right and left sides of the FN were surgically implanted with guide cannulas. Immediately after an intraperitoneal injection of acetic acid (1.00 mL, 1.00%), the first writhing onset latency and the writhing number over 60 min were recorded. Open-field and rotarod tests were applied for general locomotor and motor coordination assessment, respectively. Histamine and dimaprit (H2 receptor agonist) increased first writhing onset latency, decreased the writhing number and increased falling time from the rod. These effects were prevented by ranitidine (H2 receptor antagonist) pre-treatment. Significant alterations were not observed by histamine H1 receptor agonist (2-pyridylethylamine) and antagonist (mepyramine). Naloxone, with no effect on falling time from the rod, inhibited the antinociceptive effects of histamine and dimaprit. Beam break number was not affected by the above-mentioned treatments. Based on the results, it can be suggested that histamine H2, but not H1 receptors at the FN might have had an inhibitory role on acetic acid-induced visceral pain and improved motor coordination. The antinociception, but not motor coordination might be mediated by FN opioid receptors.