Systemic Interplay of BDNF and Serotonin Pathways Defines Behavioral and Molecular Responses to Midbrain 5-HT7 Overexpression and Chronic Ethanol Consumption.

ABSTRACT: Chronic ethanol exposure and genetic factors interact to drive neuroadaptations in alcohol use disorders (AUD). However, the system-level coordination of molecular responses across brain regions remains unclear. The 5-HT system and BDNF are key regulators of neuroplasticity in alcoholism. The 5-HT₇ receptor modulates both behavior and serotonin signaling. We investigated midbrain 5-HT₇ overexpression in C57BL/6 mice given 5-week ethanol access. Our results showed complex, region-specific changes in 5-HT and BDNF signaling, as well as selective behavioral alterations. Ethanol abolished the antidepressant-like effect of 5-HT₇ overexpression and increased anxiety-like behavior, without affecting baseline locomotion or novel object recognition. At the molecular

SUBMITTER: Rodnyy A 

PROVIDER: S-EPMC12838814 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature