Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 3 2025 09 20 162 170 Akram Molamohammadi Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran Marzieh Dehghan Shasaltaneh Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran Nasser Naghdi Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Rasool Hemayattalab Department of Sports Injuries and Corrective Exercises, University of Tehran, Tehran, Iran Hassan Gharayagh Zandi Department of Sports Injuries and Corrective Exercises, University of Tehran, Tehran, Iran 2025 08 16 2025 10 27 Objectives: Learning is essential for nearly all aspects of human behavior and perception. Among the factors that can disrupt learning and memory, stress is particularly significant, as it interferes with cognitive functioning and overall well-being. The present study aimed to evaluate and compare the effects of citalopram, treadmill-based aerobic exercise, and swimming on learning and memory performance in male Wistar rats exposed to stress. Methods: To assess these interventions, animals were subjected to immobility stress, moderate-intensity treadmill running, swimming exercise, or citalopram administration (10 mg/kg body weight for four weeks), as well as various combinations of these interventions under stressed and non-stressed conditions, but citalopram was assessed in the presence of stress. The Morris water maze test was used to assess cognitive performance, particularly by measuring the distance traveled to reach the hidden platform. Results: The results revealed that stress negatively impacted learning and memory. However, both forms of exercise alleviated stress-induced cognitive impairments, with swimming showing especially beneficial effects in enhancing learning and memory among stressed rats. Conclusion: Contrary to expectations, administration of citalopram did not prevent stress-induced cognitive dysfunction. However, the beneficial effects of both forms of exercise were evident during the acquisition phase. Notably, physical exercise—particularly swimming—may serve as a potential non-pharmacological substitute, as its cognitive effects under stress differed significantly from those of treadmill training in the presence of citalopram. https://abi.tums.ac.ir/index.php/abi/article/view/151 https://abi.tums.ac.ir/index.php/abi/article/download/151/115