Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience

• Published in: Biomolecules (Basel, Switzerland) Vol. 13; no. 5; p. 806
• Main Authors: Savchenko, Artem, Targa, Giorgia, Fesenko, Zoia, Leo, Damiana, Gainetdinov, Raul R, Sukhanov, Ilya
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-05-2023; MDPI
• Subjects: Animals; Attention deficit hyperactivity disorder; Autism; Bipolar disorder; Brain; Carrier proteins; Cognitive ability; Corpus Striatum - metabolism; Development and progression; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine receptors; Dopamine transporter; dopamine transporter knockout rodents; Gene mutations; Genetic aspects; Health aspects; Hyperactivity; hyperdopaminergia; hypodopaminergia; locomotor hyperactivity; Membrane proteins; Mutation; Neostriatum; Nervous system; Nervous system diseases; Neural transmission; Neurological research; Neurotransmission; Parkinson's disease; Phosphorylation; Physiological aspects; Proteins; Review; Rodentia - metabolism; Rodents; Synaptic Transmission; Russia; hyperdopaminergia; hypodopaminergia; dopamine transporter; dopamine transporter knockout rodents; locomotor hyperactivity
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13050806

The key element of dopamine (DA) neurotransmission is undoubtedly DA transporter (DAT), a transmembrane protein responsible for the synaptic reuptake of the mediator. Changes in DAT's function can be a key mechanism of pathological conditions associated with hyperdopaminergia. The first strain of gene-modified rodents with a lack of DAT were created more than 25 years ago. Such animals are characterized by increased levels of striatal DA, resulting in locomotor hyperactivity, increased levels of motor stereotypes, cognitive deficits, and other behavioral abnormalities. The administration of dopaminergic and pharmacological agents affecting other neurotransmitter systems can mitigate those abnormalities. The main purpose of this review is to systematize and analyze (1) known data on the consequences of changes in DAT expression in experimental animals, (2) results of pharmacological studies in these animals, and (3) to estimate the validity of animals lacking DAT as models for discovering new treatments of DA-related disorders.