Suggesting a possible role of CA1 histaminergic system in harmane-induced amnesia.
A number of tremorogenic β-carboline alkaloids such as harmane are naturally present in the human food chain. They are derived from medicinal plants such as Peganum harmala that have been used as folk medicine in anticancer therapy. In the present study, effects of the histaminergic system of the dorsal hippocampus (CA1) on harmane-induced amnesia were examined. One-trial step-down was used to assess memory retention in adult male mice. The results showed that pre-training intra-CA1 administration of histamine (5μgmouse), ranitidine (H2 receptor antagonist at the doses of 0.25 and 0.5μgmouse) and pyrilamine (H1 receptor antagonist at the dose of 5μgmouse) decreased memory formation. Pre-training intraperitoneal (i.p.) administration of harmane (12mgkg) also decreased memory formation. Moreover, pre-training intra-CA1 injection of a sub-threshold dose of histamine (2.5μgmouse) could reverse harmane (12mgkg, i.p.)-induced impairment of memory. On the other hand, pre-training intra-CA1 injection of sub-threshold doses of ranitidine (0.0625μgmouse) and pyrilamine (2.5μgmouse) increased harmane-induced impairment of memory. In conclusion, the present findings suggest the involvement of the CA1 histaminergic system in harmane-induced impairment of memory formation.