This study investigated the effects of voluntary and involuntary/regular exercise on neurotrophic factors in the brain, cognitive functions, and anxiety in socially isolated adolescent male rats. In this study, 42 adolescent male Sprague-Dawley rats were divided into six groups: control (C), socially isolated (SI), voluntary exercise (VE), regular exercise (RE), socially isolated + voluntary exercise (SI-VE), and socially isolated + regular exercise (SI-RE). Socially isolated groups were kept in separate cages for 4 weeks. Treadmill and wheel running were used in the exercise groups. The following behavioral tests-elevated plus maze (EPM), open field, ultrasonic vocalization (USV), and Morris water maze (MWM)-rats were euthanized, and brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) levels were measured in the prefrontal cortex (PFC) and hippocampus. Statistically, the differences between the groups were evaluated by one-way ANOVA and post hoc LSD tests using IBM SPSS software. In the EPM, locomotor activity was higher in the voluntary exercise groups. In the MWM, both regular exercise groups found the platform faster. In the USV, the SI-RE group produced more 50-kHz sounds. BDNF and NGF levels in the hippocampus were higher in the SI-RE and SI-VE groups
VEGF levels were higher in the SI-RE group. Neuron density in the PFC increased in the SI-RE and VE groups, while neuron density in the hippocampus increased in the SI-RE, SI-VE, and VE groups. According to the findings, we showed that voluntary exercise reduces social isolation-induced anxiety, and involuntary/regular exercise both reduces anxiety and has potential benefits on cognitive functions.