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Environmental Factor, January 2012

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Distinguished lecturer discusses the mechanism of action of amphetamine

By Anshul Pandya

Susan Amara, Ph.D. at the podium

“The key is to understand the functioning of the transporters of neurotransmitters in the brain, so that they can be targeted by new drugs to treat psychiatric disorders,” Amara said. (Photo courtesy of Steve McCaw)

The packed auditorium

Amara engaged the audience with intriguing information about the action of amphetamine on a cellular level and the pathways involved. (Photo courtesy of Steve McCaw)

Neuroscientist Susan Amara, Ph.D., delivered the latest talk in the NIEHS Distinguished Lecture Series Dec. 13, 2011, with a presentation focused on the mechanism of action of amphetamine on dopamine and glutamate transporters. These transporters are responsible for the clearance of the neurotransmitters dopamine and glutamate following their release at sites of neuronal communication in the nervous system known as synapses.

Amara specializes in the structure and function of brain neurotransmitter transporter proteins and is the Thomas Detre professor and chair of neurobiology at the University of Pittsburgh. She is also the most recent past president of the Society for Neuroscience, the largest organization of neuroscientists in the world. NIEHS lead researcher Jerrel Yakel, Ph.D., hosted the talk.

Her current research is focused on elucidating the biochemical pathways that mediate dopamine transporter internalization by amphetamine. Understanding this mechanism is important because the dopamine transporter serves as a target for a variety of clinically used medications and recreationally abused drugs.

The actions of amphetamine

“While reuptake inhibitors of serotonin, norepinephrine, and dopamine are widely used clinically to treat depression,” Amara said, “we know much less about the mechanism of action of amphetamines, which also target the three biogenic amine transport systems.” In her talk, Amara stressed that cocaine and amphetamines, both commonly abused psychostimulants, have different actions on the dopamine transporter.

Cocaine inhibits the dopamine transporter at the cell surface, whereas amphetamine, in addition to being an inhibitor of the dopamine transporter, enters the neurons. Amara’s research has found that once it enters neuronal cytoplasm, amphetamine activates intracellular signaling pathways and causes the internalization of the dopamine transporter.

Near the end of her talk, Amara described the action of amphetamine on a neuronal glutamate transporter. Similar to its effect on the dopamine transporter, amphetamine also causes the internalization of the glutamate transporter. She went on to show experimental data suggesting that in order for amphetamine to mediate the internalization of the glutamate transporter, the transporter requires a particular stretch of five amino acids that are located in the C-terminus or near the end of its protein structure. Removing these amino acids blocks glutamate transporter internalization by amphetamine.

Interaction with NIEHS postdocs

After her lecture, Amara joined NIEHS postdoctoral fellows for a brown bag lunch. It was an opportunity for these young scientists to tell Amara about their own research interests and seek her advice regarding their careers. Amara briefly spoke about her research and career progression, and about the prospects of research funding for biomedical science in the current budgetary environment. She also mentioned her lobbying effort with Congress during her tenure as the president of the Society for Neuroscience, in favor of keeping research funding at current levels.

(Anshul Pandya, Ph.D., is an Intramural Research Training Award fellow in the NIEHS Laboratory of Neurobiology Ion Channel Physiology Group.)

Audience Members

Audience members listened to the Amara talk with keen interest. From left to right, Thomas McCormack, Ph.D., Christian Erxleben, Ph.D., Ezequiel Marron, Ph.D., Bernd Gloss, Ph.D., Erica Scappini and Fengxia Mizuno, Ph.D.s (Photo courtesy of Steve McCaw)

Susan Amara, Ph.D. and Jerrel Yakel, Ph.D. answering questions after the lecture

Amara and Yakel listened to questions raised by audience members after the talk. (Photo courtesy of Steve McCaw)

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