Thioperamide, a histamine H-3 receptor antagonist, increases GABA release from the rat hypothalamus

Using a microdialysis method and a new high performance liquid chromatography (HPLC)-fluorometric method for the detection of gamma-aminobutyric acid (GABA), we investigated the effect of thioperamide, on H-3 receptor antagonist, on the GABA content in the dialysate from the arterior hypothalamic area of rats anesthetized with urethane. The addition of thioperamide to the perfusion fluid increased the release of GABA and histamine. Depleting neuronal histamine with alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, and the administration of immepie, on H-3 agonist, had no effect on basal- and thioperamide-induced GABA release. In addition, an infusion of clobenpropit, the most specific H-3 receptor antagonist available, did not alter the basal release of GABA. On the other hand, histmine release was decreased by immepip and increased by diaperamide and clabepropit. Removing Ca2+ from the perfusion fluid did not alter the effect of thioperamide on the GABA release, whereas that on histamine release was abrogated. These results suggest that the effect of thioperamide on GABA release is not mediated by histamine H-3 receptors, and that thioperamide acts on the transporter to cause an efflux of GABA from neurons and/or glia. thioperamide is a popular H-3 receptor antagonist which has been used applied to many studies. However, results using this compound should be interpreted in consideration of its effects on GABA release.