Anxiety-like behavior induced by histaminergic agents can be prevented by cannabinoidergic WIN55,212-2 injected into the dorsal hippocampus in mice

In the present study, we investigate the effects of the histaminergic system and cannabinoid receptor agents on anxiety-related behaviors and their interactions using the hole-board test on mice. Bilateral intra-CA1 administration of the CB1/CB2 receptor agonist, WIN55, 212-2 (0.1–0.5 µg/mouse) did not modify exploratory behaviors in mice. On the other hand, intra-CA1 administration of CB1 receptor antagonist, AM251 (25 and 50 ng/mouse) or histamine, pyrilamine and ranitidine (5–10 µg/mouse) decreased the amount of head-dipping and increased the first head-dip, suggesting an anxiogenic-like response. Furthermore, our present data indicated that the co-administration of WIN55, 212-2 (0.25 µg/mouse) with histaminergic agents, decreased the anxiogenic-like response of an effective dose (5 µg/mouse) of histamine and pyrilamine, but not that of ranitidine. In addition, the results demonstrated that co-administration of an ineffective dose of AM251 (15 ng/mouse) with histaminergic drugs did not alter the response induced by an ineffective dose (3.75 µg/mouse) of either histamine or pyrilamine and ranitidine. In all experiments and doses, locomotor activity and other exploratory behaviors were not significantly changed. In conclusion, our results showed that there is a chance of partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiogenic/anxiolytic-like behaviors in hole-board test.