D1-D2 receptor heteromer interfering peptide

The **D1-D2 receptor heteromer interfering peptide** (commonly referred to as **TAT-D1**) is a synthetic, cell-penetrating peptide designed to selectively disrupt the physical interaction between the dopamine D1 and D2 receptors. These receptors can form a functional Gq-coupled D1-D2 receptor heteromer, which triggers intracellular calcium signaling cascades and downstream pathways linked to behavioral aversion, depression, and anxiety. Developed by researchers at the **University of Toronto** and the **Centre for Addiction and Mental Health (CAMH)**, the peptide mimics the carboxyl tail sequence of the D1 receptor (specifically containing the critical 404Glu and 405Glu residues) that binds to the D2 receptor. By preventing heteromerization, TAT-D1 inhibits the unique Gq-mediated calcium signaling and downstream cascades (such as BDNF/TrkB and Akt/GSK3/β-catenin). In preclinical rodent models, intranasal or intracerebroventricular administration of the peptide reverses chronic unpredictable stress-induced depressive- and anxiety-like behaviors, including anhedonia, without affecting basal locomotor activity.

Other names

D1-D2 heteromer-disrupting peptideD-1-D2 heteromer-disrupting peptideD 1-D2 heteromer-disrupting peptideD1-D2 interfering peptideD-1-D2 interfering peptideD 1-D2 interfering peptideTAT-D1-CTTAT-D-1-CTTAT-D 1-CT