The selective 5-HT_1A receptor silencer Freud-1 is known as one of the main factors participating in the transcriptional regulation of the serotonin brain 5-HT_1A receptor. However, the role of Freud-1 in the mechanisms of genetically determined or exposed to experimental modification 5-HT_1A receptor brain system in vivo still remains a mystery. Variations in the 5-HT_1A receptor gene expression in the brain of two inbred mouse lines, AKR and CBA, were discovered by our group, while no difference in the Freud-1 gene expression in these lines was observed. No difference in the primary and secondary structure of Freud-1 binding site (DRE-element) was found in CBA and AKR mouse lines. This indicates the lack of distinctions in the Freud-1 binding site to 5-HT_1A receptor gene promoter in analyzed lines. It has been shown that 5-HT_1A receptor gene expression significantly decreased in the mesencephalon together with substantial increase in Freud-1 gene expression in the model simulated 5-HT_1A receptor desensitization under its chronic activation. The data permit us to conclude that 5-HT_1A receptor selective silencer is involved in the compensatory mechanisms system regulating the serotonin system status in the brain. However, the selective silencer is not the only factor in the transcriptional regulation of 5-HT_1A receptor.