Lucia Carvelli, an assistant professor in the department of basic science in the University of North Dakota School of Medicine, will present her research on the function of amphetamine. Her presentation “Amphetamine and Its Multiple targets: an in vitro and in vivo study” will be given 4-5p.m. Thursday, April 23, in Moulton Hall, room 201.
Abstract of her presentation
Amphetamine is a psychostimulant, which is thought to generate its effects by promoting release of dopamine through reverse activation of the dopamine transporters. However, some amphetamine-mediated behaviors persist in dopamine transporters knock out animals. These results suggest the existence of alternative targets of amphetamine.
We use C. elegans to look for new amphetamine targets and to study the mechanism of action of amphetamine. We found that a large fraction of the behavioral effects of amphetamine is mediated by activation of the newly identified amine-gated chloride channel LGC-55. Our in vitro and in vivo results demonstrate that in C. elegans amphetamine alters locomotion by both increasing the extracellular dopamine levels through the dopamine transporter and by activating the LGC-55 channels. Furthermore, our data demonstrate that the endogenous trace amine β-phenylethylamine (βPEA) activates the LGC-55 channels and alters locomotion more efficiently than amphetamine.
Interestingly we found that amphetamine potentiates the activation of the LGC-55 by βPEA both in in vitro and in vivo experiments. Since βPEA is an endogenous amine, our data support the hypothesis that amphetamine interferes with the endogenous activation of LGC-55 by βPEA. These findings uncover alternative pathways engaged by amphetamine, and urge rethinking of the molecular mechanisms underlying the effects of this highly addictive psychostimulant drug.
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