[Effects of Histamine and Related Compounds on the Central Nervous System]

There has been little information about the role of histamine on the central nervous system (CNS), different from dopamine and serotonin. In the present study, therefore, the effects of histamine and related compounds on the CNS were studied using rats. Intracerebroventricular (i.c.v.) injection of histamine and 2-methylhistamine ameliorated memory deficit after long interrution of learning in active avoidance response. First generation H₁-antagonists inhibited active avoidance response, whereas newly develpoed H₁-antagonists showed little effect. α-Fluoromethylhistidine, an histidine decarboxylase inhibitor, also inhibited active avoidance response. In radial maze performance, almost the same findings were obtained. I.c.v. injection of histamine and H₁-agonists inhibited amygdaloid kindled seizures. First generation H₁-antagonists attenuated histamine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and intraperitoneal injections of H₃-antagonist, thioperamide, resulted in a dose-related inhibition of amygdaloid kindled seizures. The effect of thioperamide was inhibited by an H₃-agonists and H₁-antagonists. Similar to nitrazepam, diphenhydramine and chlorpheniramine caused a shortening of sleep latency. On the other hand, no significant effects were observed with second generation H₁-antagonists. These findings suggest that histamine plays an important role in learning and memory via H₁-receptors, an inhibition of amygdaloid kindled seizures induced by histamine occurred through not only H₁-receptors but also H₃-receptors, and that classic H₁-antagonists can be useful as a effective hypnotic for difficulty in falling asleep.