Background: β-carboline alkaloids, such as harmane, are found in common plant-derived foodstuffs and plant-derived inhalation components of tobacco. In the present study, the involvement of dorsal hippocampus nicotinic receptor in the harmane effects on anxiety behavior has been evaluated.

Materials and Methods: Mice were anesthetized with an intra-peritoneal injection of ketamine hydrochloride plus xylazine and then placed in a stereotaxic apparatus. Cannual were bilaterally implanted in the CA1 region of hippocampus. All animals were allowed to recover for 1 week before the beginning of the behavioral testing. The hole-board test was used to evaluate the anxiety-like behaviors. One-way analys was of variance so that Dunnett’s test was used to analyse data. All experiments were performed in accordance with institutional guidelines for animal care and use.

Results: Intraperitoneal injection of harmane decreased the number of head dip and locomotion (P<0.001). While bilateral intra-dorsal hippocampal injections of nicotine decreased the number of head dip (P<0.01), it had no effect on locomotor activity. Furthermore, intra-dorsal hippocampal injection of mecamylamine (nicotinic receptor antagonist) in the presence and absence of harmane had no effect on anxiety behavior and locomotion (P>0.05).

Conclusion: harmane and nicotine not only display anxiogenic effects but also demonstrate a complex interaction. The findings also indicated that harmane induces anxiety via non-nicotinic receptors.