D1R-5-HT2AR Uncoupling Reduces Depressive Behaviours via HDAC Signalling.

ABSTRACT: Dopamine and serotonin signalling are associated with major depressive disorder, which is a prevalent life-threatening illness worldwide. Numerous FDA-approved dopamine/serotonin signalling-modifying drugs are available but are associated with concurrent side effects and limited efficacy. Thus, identifying and targeting their signalling pathway is crucial for improving depression treatment. Here, we determined that serotonin receptor 2A (5-HT2AR) abundantly forms a protein complex with dopamine receptor 1 (D1R) in high abundance via its carboxy-terminus in the brains of mice subjected to various chronic stress paradigms. Furthermore, the D1R/5-HT2AR interaction elicited CREB/ERK/AKT modulation during synaptic regulation. An interfering peptide (TAT-5-HT2AR-SV) agitated the D1R/5-HT2AR inte

SUBMITTER: Li W 

PROVIDER: S-EPMC10684469 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature