Experimental modeling and revealing of neuromodulation on central monoaminergic systems of environmental and lifestyle factors were realized. 3 groups of laboratory animals (rats): control (n=5); forced physical activity during the resting period (n=5); forced physical activity with the consumption of hedonic food (n=5) were used. Forced physical activity during the resting period (shift work modeling) was simulated by a rotating cage. The hedonic food consumption included the preferred aliments in the diet. The concentration of monoamines and their metabolites was estimated by high-performance liquid chromatography. In the prefrontal cortex (PFC) after forced physical activity the norepinephrine concentration significantly increases compared to control group (by 36.7%, P<0.01). The serotonin concentration increase in the PFC was less pronounced (by 17.9%, P<0.05) and associated with the dopamine concentration decrease (by 23, 2%, P<0.05) and reduced homovanillic acid concentration (by 21.8%, P<0.05). In order to optimize physical activity its duration was limited up to 240 min and combined with the intake of palatable food. Optimization scheme induced a significant increase in the dopamine concentration increase (by 27.5%, P<0.01) in the PFC, compared with the group of non-optimized animals. Optimization revealed an elevation of the level of serotonin in the hippocampus on the background of a decrease in the concentration of 5-hydroxyindoleacetic acid. Forced wakefulness activates the NE-ergic system and suppresses the DA-ergic system, which provides the effect of reinforcement and the formation of motivation. Physical activity optimization allows leveling the created imbalance of centripetal neuromodulatory action on the cerebral cortex and hippocampus.