Dopamine transporter knockout rats as the new preclinical model of hyper- and hypo-dopaminergic disorders

Abstract

Rat line lacking the dopamine transporter (DAT-KO rats) was recently developed. Lack of DAT in these mutants manifests behaviorally as spontaneous hyperactivity and cognitive deficits. It has been shown that d-amphetamine and methylphenidate paradoxically calm down these animals. Also, the inhibition of dopamine synthesis in DAT-KO rats represents a straightforward approach for developing the model of severe dopamine deficiency exhibiting characteristic akinetic phenotype which can be reversed by treatment with L-DOPA that used in Parkinson’s disease. These results support the usefulness of DAT-KO rats as models of the disorders associated with dopaminergic dysfunction.