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Medical Science Monitor Basic Research


eISSN: 1643-3750

The Effects of Oxytocin on Cognitive Defect Caused by Chronic Restraint Stress Applied to Adolescent Rats and on Hippocampal VEGF and BDNF Levels

Ayfer Dayi, Ferihan Cetin, Ali Riza Sisman, Ilkay Aksu, Aysegul Tas, Sevil Gönenc, Nazan Uysal

Department of Physiology, School of Medicine, Dokuz Eylul University, Izmir, Turkey

Med Sci Monit 2015; 21:69-75

DOI: 10.12659/MSM.893159

Available online:

Published: 2015-01-06


Background: Because brain development continues during adolescence, the effects of chronic stress on hippocampal changes that occur during that period are permanent. Oxytocin, which is synthesized in the hypothalamus and has many receptors in brain regions, including the hippocampus, may affect learning-memory. This study aimed to investigate chronic restraint stress on hippocampal functions, and hippocampal vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in adolescent male and female rats and the role of oxytocin in these effects.
Material and Methods: Experimental groups included control, stress+oxytocin, and stress+saline groups. Restraint stress was applied to all the stress groups for 1 h/day, for 7 days. Learning-memory tests were performed after the 7th day.
Results: In the stress+oxytocin groups, the process of finding the platform was shorter than in others groups. The stress+saline groups spent less time, whereas the stress+oxytocin groups spent more time, on the target quadrant in the probe trial. In the stress+oxytocin groups thigmotaxis time (indicating anxiety) decreased, but VEGF and BDNF levels increased. A positive correlation was found between VEGF and BDNF levels and the time spent within the target quadrant.
Conclusions: The results indicate that impaired hippocampal learning and memory loss due to chronic restraint stress can be positively affected by intranasal oxytocin.

Keywords: Cognition Disorders - drug therapy, Brain-Derived Neurotrophic Factor - metabolism, Anxiety, Animals, Hippocampus - metabolism, Hypothalamus - drug effects, Learning - drug effects, Maze Learning, Memory - drug effects, Oxytocin - therapeutic use, Rats, Rats, Wistar, Vascular Endothelial Growth Factor A - metabolism