Effects of Memantine on the Spontaneous Firing Frequency of Hippocampal CA1 Pyramidal Neurons in Intact and Alzheimer Rat Model: An Electrophysiological Study

Abstract

Introduction: Memantine (MEM) is a noncompetitive NMDAR antagonist clinically used for the treatment Alzheimer’s disease (AD) in mild to severe conditions. The present study was conducted to investigate the effects of Memantine on the spontaneous firing frequency of CA1 pyramidal neurons in rats with electrical lesion of nucleus basalis magnocellularis (NBM) as an animal model of Alzheimer's disease compared with intact adult males. Methods: In this study, adult male rats were divided into two groups. Group I (Lesion NBM, n=53) includes the following subgroups: Lesion+Saline; Sham+Saline; Lesion+MEM5mg/kg; Lesion+MEM10mg/kg; Lesion+MEM20mg/kg. And Group II (Intact, n=48) include the following subgroups: Intact+Saline; Intact+MEM3mg/kg; Intact+MEM5mg/kg; Intact+MEM10mg/kg. Extracellular single unit recording (15 min baseline+105 min after MEM or saline) was performed under urethane-anesthetized rats. Results: The results showed that the mean frequency of CA1 pyramidal neurons after saline in the Lesion+Saline (P<0.001) group significantly decreases compared with the Intact+Saline and Sham+Saline groups. In addition, after saline and memantine, the mean frequency of CA1 pyramidal neurons in the Lesion+MEM10mg/kg (P<0.01) and Lesion+MEM20mg/kg (P<0.001) groups significantly increases compared with the Lesion+Saline group. In addition the mean frequencies of CA1 pyramidal neurons in the Intact+MEM10mg/kg (P<0.001) group significantly decreases compared with the intact+saline group. Conclusion: Results showed that memantine increases the electrical activity of CA1 pyramidal neurons in rats model of Alzheimer's disease. Furthermore, in intact adult male rats, it was shown that low-dose memantine contrary to its high dose not decrease the electrical activity of CA1 pyramidal neurons.

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“…In another study, memantine, which is also an NMDA receptor antagonist, was found to significantly decrease the electrical activity of CA1 pyramidal neurons in an Alzheimer's rat model. This study also demonstrated that memantine had different effects on the firing rate of CA1 pyramidal neurons in intact and lesioned rats, with some neurons being unaffected, excited, or inhibited [ 68 ]. Another study indicated that reduced NMDA receptor function has contrasting impacts on prefrontal cortex interneurons and pyramidal neurons.…”