Abstract

Objectives: We investigated the role of central histaminergic system on learning and memory functions in mice and rats.

Study Design: Learning and memory functions were investigated using elevated plus-maze test in mice and radialarm maze test in rats. The mice were placed in the maze for 60 seconds on the first day to allow them to learn the maze. Twenty-four hours later, they were put in the maze again to record the time spent to enter one of the closed arms. The effects of pyrilamine, ranitidine, thioperamide and histidine injected one hour before the test were examined in diverse groups of mice whose memory functions were intact or impaired by scopolamine injection 15 minutes before the test. In the radial-arm maze test, the rats were allowed to find food placed in four arms of the maze for seven days. On the eighth day, diverse groups were assigned to receive pyrilamine, ranitidine, thioperamide, histamine, and histidine. Histidine and histamine were also given following induction of tuberomammillary nucleus lesions and the modulation of histamine effects by pyrilamine, ranitidine, and thioperamide was tested.

Results: Pyrilamine, ranitidine, thioperamide, histidine, and histamine had no effect on memory functions. Histidine increased memory retention in mice with scopolamine-induced deficits in elevated plus-maze performance; this effect was blocked by pyrilamine, but not affected by ranitidine and thioperamide. In rats with tuberomammillary nucleus region lesions, prolongation of the completion period of the test and working memory failures were observed; but there were no changes on reference memory failures. These deteriorations were improved by histamine and histidine. The enhancing effect of histamine on memory was antagonized by pyrilamine, but remained unchanged by ranitidine and thioperamide.

Conclusion: These results show that central histaminergic system has an enhancing effect on memory function and this effect is mediated by histamine H1 receptors.