The brain's serotonin (5-HT) system plays an important role in the control of normal and pathological behavior. 5-HT_2A receptors are widely implicated in the regulation of normal brain functions and in the pathogenesis of mental disorders, especially schizophrenia and depression. In this work, we studied the involvement of 5-HT_2A receptors in the action of the brain-derived neurotrophic factor (BDNF) and the glial cell line-derived neurotrophic factor (GDNF). It was found that an acute intracerebroventricular BDNF injection caused a considerable increase in the functional activity of 5-HT_2A receptors in ASC mice genetically predisposed to depression-like behavior. Moreover, as a result of the administration of BDNF, the expression of the 5-HT_2A receptor gene increased in the hippocampus, decreased in the frontal cortex, and did not change in the midbrain. In contrast, GDNF administration did not affect the functional activity of 5-HT_2A receptors, but increased the expression of the 5-HT_2A receptor gene in the frontal cortex, but not in the hippocampus or the midbrain. Thus, the central administration of BDNF and GDNF was shown to affect the functional activity of 5-HT_2A receptors and the expression of their genes. These results indicate that 5 HT_2A receptors can be involved in the mechanisms of BDNF and GDNF action.