Overview of Interests
Once released into the synaptic cleft, neurotransmitters such as dopamine and norepinephrine must be cleared to control the magnitude and duration of synaptic signaling. Neurotransmitter transporters are mainly responsible for this clearing process. These integral membrane proteins transport neurotransmitter back into the neuronal terminals, thereby terminating synaptic signaling. Substances of abuse such as cocaine and amphetamine or drugs with important clinical relevance including antidepressants act upon these transporters to ultimately increase the concentration of dopamine and norepinephrine in the synaptic cleft. Using site-directed mutagenesis on norepinephrine and dopamine transporters, we are trying to identify the regions of the transporter involved in the recognition of their substrates. Our goal is to identify the transporter structural domains conferring pharmacological specificity to amphetimines and cocaine. Finally, using electrophysiological techniques, we are characterizing new functional aspects of dopamine and norepinephrine transporters involved in the mechanism of action of amphetamine and cocaine. The results of this research will help in developing new strategies and molecules for the treatment of psychiatric disorders and substance abuse.
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