The trafficking of synaptic proteins is unquestionably a major determinant of the properties of synaptic transmission. Here, we present a detailed analysis of the downregulation and intracellular trafficking of the cocaine- and amphetamine-sensitive dopamine transporter (DAT), a presynaptic plasma membrane protein responsible for the regulation of extracellular DA concentrations. Using PC12 cel...

Impulsivity, the predisposition to act without regard for negative consequences, is a characteristic of several psychiatric disorders and is thought to result in part from genetic variation in the untranslated region of the dopamine transporter (DAT) gene. As the exact link between genetic mutations and impulsivity has not been established, we used oculomotor behavior to characterize rhesus mon...

The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft and is a target for widely abused psychostimulants such as cocaine and amphetamine. Nonetheless, little is known about the cellular distribution and trafficking of natively expressed DAT. Here we use novel fluorescently tagged cocaine analogs to visualize DAT and DAT trafficking in cultured live midbrain dopami...

The dopamine transporter (DAT) regulates extracellular dopamine concentrations, transports neurotoxins, and acts as a substrate for cocaine reinforcement. These functions are known to differ in the limbic-associated shell and motor-associated core compartments of the nucleus accumbens (NAc). Previous studies have shown differential expression of DAT in the NAc shell and core but were limited in...

The plasma membrane dopamine (DA) transporter (DAT) is essential for reuptake of extracellular DA. DAT function in heterologous cells is regulated by subcellular targeting, endocytosis, and intracellular trafficking, but the mechanisms regulating neuronal DAT remain poorly understood. Hence, we generated a knock-in mouse expressing a hemagglutinin (HA)-epitope-tagged DAT to study endogenous tra...

OBJECTIVES To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow com...

We compare an inverse-planning intensity-modulated radiotherapy (IMRT) technique with three previously published forward-planning dynamic arc therapy techniques and a newly implemented technique for treatment of prostate only. The three previously published dynamic arc techniques are dynamic arc therapy (DAT), two-axis dynamic arc therapy (2A-DAT), and modified dynamic arc therapy (M-DAT). The ...

The regulation of the dopamine transporter (DAT) impacts extracellular dopamine levels after release from dopaminergic neurons. Furthermore, a variety of protein partners have been identified that can interact with and modulate DAT function. In this study we show that DJ-1 can potentially modulate DAT function. Co-expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [3H] dopamin...

The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action...