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The dopamine transporter, DAT, is a primary regulator of dopamine (DA) signaling at the synapse. Persistent stimulation with the substrate amphetamine (AMPH) promotes DAT internalization. AMPH rapidly elicits DA efflux, yet its effect on DAT trafficking at short times is unknown. We examined the rapid effect of AMPH on DAT trafficking in rat striatal(More)
Although it is clear that amphetamine-induced dopamine (DA) release mediated by the dopamine transporter (DAT) is integral to the behavioral actions of this psychostimulant, the mechanism of this release is not clear. In this study, we explored the requirement for intracellular Ca(2+) in amphetamine-induced DA efflux and currents mediated by the human DAT.(More)
The dopamine transporter (DAT) is a key mediator of dopaminergic neurotransmission and a major target for amphetamine. We found previously that protein kinase C (PKC) beta regulates amphetamine-mediated dopamine efflux. Here, using PKCbeta wild-type (WT) and knockout (KO) mice, we report a novel role for PKCbeta in amphetamine-induced regulation of DAT(More)
Repeated intermittent treatment with amphetamine (AMPH) induces both neurite outgrowth and enhanced AMPH-stimulated dopamine (DA) release in PC12 cells. We investigated the role of protein kinases in the induction of these AMPH-mediated events by using inhibitors of protein kinase C (PKC), mitogen activated protein kinase (MAP kinase) or protein kinase A(More)
Rapid treatment (1 min) of rat striatal synaptosomes with low-dose amphetamine increases surface expression of the dopamine transporter (DAT). Using mouse neuroblastoma N2A cells, stably transfected with green fluorescent protein-DAT, we demonstrate the real-time substrate-induced rapid trafficking of DAT to the plasma membrane using total internal(More)
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein syntaxin 1A (SYN1A) interacts with and regulates the function of transmembrane proteins, including ion channels and neurotransmitter transporters. Here, we define the first 33 amino acids of the N terminus of the dopamine (DA) transporter (DAT) as the site of direct(More)
Inbred strains of mice have served as valuable models for studying genetic susceptibility to drug addiction, an alternative to genetically modified mouse models. This is the first study comparing amphetamine (AMPH) effects on locomotor stimulation and dopamine efflux between two inbred strains of mice C57BL/6J and 129S2/SvHsd, frequently used as background(More)
The human dopamine transporter (hDAT) regulates synaptic dopamine (DA) levels and is the site of action of abused and therapeutic drugs. Here we study the effect of a threonine residue (Thr62 in hDAT) that is highly conserved within a canonical phosphorylation site (RETW) in the juxtamembrane N-terminal region of monoamine transporters. In stably(More)
Nicotine has been demonstrated to enhance the subsequent use of illicit drugs in animals and humans. We previously demonstrated in female, Holtzman rats that one low dose of nicotine will potentiate locomotor activity and dopamine (DA) efflux in response to a subsequent low dose of d-amphetamine (AMPH) given 1-4 h later. In the present study, we show this(More)
Amphetamine and its derivatives are important drugs of abuse causing both short-term excitatory and long-term addictive effects. The short-term excitatory effects are linked to amphetamine's ability to maintain high levels of dopamine (DA) outside the cell both by inhibiting DA reuptake after synaptic transmission and by enhancing the efflux of DA from the(More)