Effect of R-(-)-α-methylhistamine and thioperamide on in vivo release of norepinephrine in the rat hippocampus

1. The modifications of hippocampal release of norepinephrine following the administration of R-(-)-alpha-methylhistamine and thioperamide, respectively agonist and antagonist of histamine H-3 receptors, were assessed in freely moving rats by microdialysis. 2. Both the systemic (2 mg/kg i.p.) and local ( 100 mu M via the probe) administration of thioperamide caused no modifications of basal release, indicating that the histaminergic system is not tonically involved in regulating the hippocampal noradrenergic activity. 3. R-(-)-alpha-methylhistamine (1 and 100 mu M) produced a slight, short-lasting and dose-dependent reduction of norepinephrine release antagonized by local perfusion (100 mu M) and prevented by systemic administration of thioperamide 2 mg/kg. 4. The results seem to indicate that the modulation of norepinephrine release through presynaptic H3-receptors in the rat hippocampus plays a minor role in the memory-enhancing effects of thioperamide.