Tat-D1 peptide is a peptide constructed from amino acids 396-413 of the dopamine D1 receptor C tail - a sequence chosen to include amino acids 404Glu and 405Glu whch were identified to interact with the dopamine D2 receptor - fused at the NH2 terminus to TAT peptide for cell permeability. TAT-D1 peptide blocks the interaction between D1 and D2 receptors, inhibiting D1-D2 heteromer expression and function without affecting other receptor oligomers such as D1-D1 homomers or D2-D5 heteromers. Tat-D1 peptide disruption of the D1-D2 heteromer abolishes its interaction with Gq and attenuates its calcium signalling and functions as a selective antagonist in vitro and in vivo. In animal models, TAT-D1 treatment alleviates behavioural despair symptoms and and exerts antidepressant-like effects in rats, and in addiction models the Tat-D1 peptide reverses SKF83959 induced inhibition of amphetamine sensitization.
