Effects of harmalol on scopolamine-induced memory disorders, anxiety and depression like behaviors in male mice: A behavioral and molecular study

Harmalol is a dihydrocarboline compound found naturally in several alcoholic beverages and medicinal plants. This study was designed to investigate the effect of harmalol on memory function and its possible mechanisms in a scopolamine-induced memory disorder model.

Thirty five male mice were randomly divided into five (n=7) group: Control group )normal saline(, scopolamin   group (scopolamine at a dose of 1 mg / kg)  and treatment groups (harmalol in three doses of 5, 10 and 20 mg / kg with scopolamine) for 21 days.  Behavioral tests were performed after the treatment period. The mice were then subjected to deep anesthesia and blood and brain tissue samples were obtained.

Harmalol significantly decreased latency to reach the hidden platform in spatial memory test and secondary latency in passive avoidance memory test and immobility time in the forced swimming test compared to scopolamine group (P < 0.05). This compound, at the dose of 20 mg/kg, showed a significant increase in the number of crossing and standing on two legs in open field test (P < 0.05). Furthermore, harmalol treatment decreased brain malondialdehyde and nitric oxide  levels, enhanced the total antioxidant capacity, and also increased the level of brain-derived neurotrophic factor (BDNF)  in the hippocampus (P < 0.05).

The present study emphasizes that harmalol improves scopolamine-induced memory loss by modulating acetylcholinesterase activity and increasing BDNF in the hippocampus of  mice. Therefore, harmalol may be a promising therapeutic drug to prevent amnesia and cognitive deficits associated with aging or neurodegenerative diseases such as Alzheimerchr('39')s.