Brain serotonin (5-HT) system plays an important role in the control of normal and pathological behavior. 5-HT2A receptors are widely implicated in the regulation both normal functions and psychopathologies, especially schizophrenia and depression. Here, we investigated implication of 5-HT2A receptor in mechanisms of neurotrophic factors BDNF and GDNF action. We found that the acute intracerebroventricular injection of BDNF produced considerable increase in 5-HT2A receptor functional activity in ASC mice. Moreover, BDNF injection led to the increasing of 5-HT2A receptor gene expression in the hippocampus and its decrease in the frontal cortex without any effects in the midbrain. On the contrary, GDNF injection failed to alter 5-HT2A receptor functional activity, but increased the 5-HT2A receptor gene expression in the frontal cortex without any effects in the hippocampus and midbrain. Thus, an effect of the central administration of the neurotrophic factors BDNF and GDNF on the 5-HT2A receptor functional activity and gene expression was shown. The results indicate the implication of 5-HT2A receptor in the mechanisms of BDNF and GDNF action.