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Margaret Gnegy

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Primary Appointment: Pharmacology Department
Other PIBS Depts.: Neuroscience
PubMed Name: Margaret E. Gnegy
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The ultimate focus of my laboratory is an investigation of dopaminergic transmission. The main project in the laboratory is to examine the mechanism by which amphetamine action at the dopamine transporter is regulated by phosphorylation, particular in response to protein kinase C. Amphetamine is a substrate that the dopamine transporter, and its rewarding actions, as well as therapeutic actions, are due to its ability to reverse the transporter and pump more dopamine into the synapse. We find that protein kinase C plays a key role in this action. My lab uses a variety of in vitro and in vivo preparations to investigate this action, including knockout mice, transfected cells, and striatal preparations from rats and mice. Techniques include measurements of dopamine efflux and locomotor behavior, HPLC, labeling and quantification of membrane transporters, confocal microscopy, receptor binding, to name a few.
Another developing project is to analyze the interactions between nicotine and amphetamine. People who take small doses of amphetamine subsequently exhibit increased smoking and increased enjoyment of smoking. Conversely, even one dose of nicotine can enhance reward. A physiologically relevant dose of nicotine increases amphetamine-mediated behaviors and amphetamine-induced dopamine release in ventral striatum of rats. We are presently exploring the transmitters that regulate this activity and the biochemical underpinnings of this interaction.