The effect of Varenicline on synaptic plasticity of hippocampus in a rat model of Alzheimer's disease

Abstract

Alzheimer's disease is one of the most common causes of dementia in old age. About 50 million people around the world are suffering from dementia and 50-70% of them are suffering from Alzheimer's disease. The main cause of this disease is the failure to clear the amyloid beta peptide from the brain tissue. Amyloid beta plaques can bind to nicotinic acetylcholine receptors (nAChRs) and lead to synaptic dysfunction in the brain of these patients. The present study was conducted to investigate the effect of the administration of varenicline as an agonist of nAChRs receptors on the electrical activity and synaptic plasticity of hippocampal CA1 neurons in a rat model of Alzheimer's disease. Materials and methods: In this study, 48 adult male Wistar rats with an average weight of 250±20 g and age between 8-10 weeks were used. After a week of adaptation to the laboratory environment, the rats were randomly divided into six experimental groups of eight animals, including control, sham surgery, Alzheimer's disease model (AD), and three AD groups treated with varenicline with doses of 0.1, 1, and 3 mg/kg. AD model was induced by injecting beta amyloid into the right lateral ventricle of the brain. A day following model induction, treatment with varenicline was started. On day 14 after modeling, by placing the recording electrode in the CA1 area and the stimulation electrode in the right hippocampus's schaffer colateral pathway, the electrical activity of the neurons in the CA1 area was recorded in the presence of different doses of varenicline. Results: Compared to before high frequency stimulation, the AD, Var 0.1 and Var 3 groups did not show a significant increase in their fEPSP slope. While this change was significant for the control, sham and Var 1 groups. In addition, compared to the AD group, the slopes of fEPSP induced LTP in both the control and Var 1 groups were significantly increased (p<0.001), indicating that Var 1 administration can induce hippocampal LTP in the CA1 region. However, no significant increase in fEPSP slope was observed in the Var 0.1 and Var 3 groups compared to the AD group.