“How Self-Eating Can Be Rewarding: A Tale of a Novel Cocaine Receptor”
Dr. Maged Harraz
Johns Hopkins University
Date/Time: Thursday, February 13th, 12:40 pm
Place: Seminar Room, SC 106
Abstract: Cocaine’s stimulant effects have been studied for well over a century, yet its molecular mechanism of action has, surprisingly, never been rigorously delineated. Many laboratories have reported inhibition of biogenic amine uptake by cocaine especially dopamine. However, cocaine is a relatively weak, micromolar, inhibitor of the dopamine transporter (DAT). We now report that cocaine binds with extraordinarily high affinity to the protein BASP1, which represents a pharmacologically relevant cocaine receptor. The depletion of BASP1 prevents the psychoactive actions of cocaine. Cocaine acts through BASP1 to stimulate neuronal autophagy (a cellular homeostatic self-degradative process). Autophagy, in-turn, inhibits dopamine reuptake by selectively targeting DAT for degradation. Pharmacological inhibitors of autophagy abolish cocaine’s behavioral actions. Our elucidation of cocaine’s mode of psychoactivity may facilitate the development of therapeutic agents for drug abuse. Insofar as cocaine acts through signaling systems underlying synaptic plasticity, our findings may help elucidate features of learning and memory.
About the Speaker: Dr. Maged Harraz got his medical and master’s degrees from Suez Canal University in Egypt. Then he moved to the US and joined the University of Iowa for graduate studies. His Ph.D. work identified a novel molecular mechanism that contributes to neurodegeneration. Dr. Harraz joined Ted and Valina Dawson’s lab at Johns Hopkins University for postdoctoral training. His work focused on microRNA regulation of neuronal development, excitability and degeneration. Then, he joined the Solomon Snyder group as a research scientist where he characterized a molecular cascade that links the glutamate receptor to mTOR signaling and identified omigapil as a putative rapidly acting antidepressant. Currently, Dr. Harraz focuses on characterizing a novel high-affinity receptor for cocaine. He is the recipient of several awards such as Maryland Innovation Initiative Grant, Johns Hopkins University Discovery Awards and NARSAD Young Investigator Grant from the Brain and Behavior Foundation.