Effects of histamine and its related compounds on impairment of passive avoidance response following hippocampal lesions in rats

The effects of histamine and its related compounds on impairment of the passive avoidance response induced by hippocampal lesions were studied in rats. A remarkable impairment of passive avoidance response was observed by bilateral dorsal hippocampal lesions. Intracerebroventricular injection of histamine and intraperitoneal injection of histidine improved the impairment of passive avoidance response in hippocampus-lesioned rats. An ameliorating effect of histamine on memory impairment was mediated via H₁-receptors. H₁- agonists, 2-thiazolylethylamine and 2-pyridylethylamine, caused the same effect as histamine, whereas H₂-agonists, 4-methylhistamine and dimaprit, failed to improve the impairment of passive avoidance response. Pretreatment with H₁-antagonists, diphenhydramine and chlorpheniramine, abolished the ameliorating effect of histamine on memory impairment, but H₂-antagonists, cimetidine and ranitidine, caused no obvious effect. H₃-antagonists, thioperamide and clobenpropit, also improved the memory impairment same as histamine. This effect was blocked by H₃-agonist, (R)-α-methylhistamine and H₁-antagonist, diphenhydramine, but not by H₂-antagonist, cimetidine. Based on these findings, histamine improves the impairment of passive avoidance response induced by hippocampal lesions via H₁-receptor. Presynaptic H₃- receptor is also involved in modulation of the memory paradigm.