Effects of chronic administration of Norharmane on spatial memory in intracerebroventricular streptozotocin Rat Model of Alzheimer's Disease

Background and Objective: Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. At now Pharmacological treatments available only can slow down the progression of symptoms but can not treat the disease. It is established that benzodiazepines, and related agonists at the benzodiazepine site of GABA receptor, present anxiolytic and amnesic properties, whereas inverse agonists, such as β-carbolines, (Norharmane) could exert anxiogenic and learning-enhancing actions. This finding has now directed the focus of research on the potential use of β-carbolines as anti-AD drug. The goal of the present study was to investigate the therapeutic efficacy of Norharmon on spatial memory of streptozotocin (STZ) Rat Model of AD
Materials and Methods: 48 male wistar rates were divided into: control, STZ, STZ+ alcohol and STZ+ norharmane groups. Alcohol and Norharmane groups rats received alcohol (0.2ml) or Norharmane (1,2, 4 mg/kg, i.p.) for 4 day before training and 6day during training, 30 min. before each session of experiments. For induction of AD, STZ (3 mg/kg, i.c.v, 10 μl each) were administered bilaterally into lateral ventricles. All rates were tested spatial memory in the Morris water maze.
Results: pre-training injection of Norharmane improves spatial memory in low doses(1,2 mg/kg ) but attenuated spatial memory retention in high doses(4 mg/kg) in STZ Rat Model of AD. so that there was no significant differece between control and STZ+Norharmane (2 mg/kg) group, whereas the differece between control and STZ +Norharmane (1,4 mg/kg) groups were significant.


Conclusion: According to the findings Norharmane, in the low doses, may be effective in the treatment of Alzheimer's disease by its ability to influence the GABAergic system