Dopamine Transporter Changes in Neuropsychiatric Disorders

Abstract

Publisher Summary The highest concentrations of dopamine transporters (DATs) are found in the basal ganglia, corresponding to the amount of dopamine (DA) nerve terminals in this brain region. Numerous studies demonstrating parallel losses of DA levels and DAT after lesions of nigrostriatal DA neurons suggest that the density of DAT is an excellent marker of the structural integrity of the dopaminergic system. In vivo imaging of DAT has been performed mainly in patients with Parkinson's disease to demonstrate the marked loss of nigrostriatal DA nerve terminals in this disorder. However, positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of DAT have been shown to be useful in various other neurodegenerative disorders, including Lesch-Nyhan disease (LND), Rett syndrome, Tourette's syndrome, stimulant abuse, and progressive supranuclear palsy. A marked reduction of striatal DAT densities has been reported in methamphetamine treated animals. In baboon studies with methamphetamine treatment, a dose-related reduction in DAT densities occurs. These studies are followed by postmortem analysis of neurochemical parameters. In recent years, the synthetic amphetamine analogue methcathinone (2-methylamino-1-phenylpropanone, ephedrone, “Cat”) has emerged as a recreational drug of abuse. In animals, methcathinone, like methamphetamine, produces toxic effects on brain DA and serotonin neurons. Moreover, studies in human subjects with a history of methcathinone abuse suggest a DAT decline as well.