Kappa Opioid Receptor Antagonism Restores Phosphorylation, Trafficking and Behavior induced by a Disease Associated Dopamine Transporter Variant.

ABSTRACT: Aberrant dopamine (DA) signaling is implicated in schizophrenia, bipolar disorder (BPD), autism spectrum disorder (ASD), substance use disorder, and attention-deficit/hyperactivity disorder (ADHD). Treatment of these disorders remains inadequate, as exemplified by the therapeutic use of d-amphetamine and methylphenidate for the treatment of ADHD, agents with high abuse liability. In search for an improved and non-addictive therapeutic approach for the treatment of DA-linked disorders, we utilized a preclinical mouse model expressing the human DA transporter (DAT) coding variant DAT Val559, previously identified in individuals with ADHD, ASD, or BPD. DAT Val559, like several other disease-associated variants of DAT, exhibits anomalous DA efflux (ADE) that can be blocked by d-amphetamine and

SUBMITTER: Mayer FP 

PROVIDER: S-EPMC10187322 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature