Effects of thioperamide on the cholinergic system and the step-through passive avoidance test in mice.
We investigated the effects of thioperamide, a histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the step-through passive avoidance test in mice, and on contents of acetylcholine and choline in the brain. In a behavioral study, thioperamide (20 mg/kg) alone slightly ameliorated scopolamine-induced learning deficit, and pretreatment with zolantidine, a histamine H2-receptor antagonist, significantly enhanced the ameliorating effect of thioperamide. This enhanced ameliorating effect of thioperamide was antagonized by pyrilamine, a histamine H1-receptor antagonist and (R)-alpha-methylhistamine, a histamine H3-receptor agonist, suggesting that thioperamide showed the ameliorating effect via histamine H3 receptors and/or histamine H1 receptors. In the biochemical study, thioperamide (20 mg/kg) in combination with zolantidine (20 mg/kg) significantly increased contents of choline in most of brain regions. These findings suggest that there is a close relationship between histaminergic and cholinergic systems in the brain, and that the histaminergic system may play certain important roles in learning and memory.
Miyazaki
S
S
Biology Laboratory, Research & Development Division, Yamasa Corporation, Choshi, Chiba.
Imaizumi
M
M
Onodera
K
K
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D006633:Histamine Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010276:Parasympatholytics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006633:Histamine Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D012601:Scopolamine; C052075:thioperamide; D002794:Choline; D000109:Acetylcholine