Objective: Neurodegenerative diseases cause serious morbidity and mortality, especially with the advance of aging world population leading to the need for the development of drugs with neuroprotective action. Therefore, in the present work we evaluated the effects of treatment with memantine, an NMDA receptor blocker, on the nuclear volume of CA1 hippocampal neurons in adult rats. Method: adult male Wistar adult rats received intraperitoneal injections (i. p.) of saline solution (SAL; 1 mL/kg) or memantine (MEM; 10 mg/kg) for 30 days, with subsequent histological processing and evaluation of nuclear volume of neurons of the CA1 area. Results: the MEM group presented significant increase in nuclear volume (SAL, 231 ± 4.1 µm3, n = 5; MEM, 380 ± 5.7 µm3, n = 6; P < 0.0001). When neurons were classified in subpopulations by media of the size of their nuclei, there was prevalence of group MEM in subpopulations of 200-400 µm3 (SAL 261.47 ± 3.27 µm3 and MEM 318.94 ± 5.43 µm3; P< 0.0001), 400- 600 µm3 (SAL 439.20 ± 7.82 µm3 and MEM 479.29 ± 5.67 µm3; P < 0.05). In the 600-800 µm3 subpopulation, only the MEM group presented neurons (689.33 ± 19.55 µ m3). Conclusion: Our results indicate that memantine can change directly or indirectly the nuclear volume of neurons in the CA1 area of the hippocampus, being a drug with potential use in the prevention of neurodegenerative diseases.