Cocaine increases dopamine levels primarily by preventing the neurochemical from being transported back into its releasing cell, leaving more outside the neuron, where it contributes to the drug's euphoric effects. Dr. R. Mark Wightman and colleagues of the University of North Carolina at Chapel Hill and Dr. George Augustine of Duke University have recently shown that cocaine also can tap into an intracellular dopamine reserve pool. As far back as the 1970s, some researchers suspected this could occur, but they could not confirm it. Now, thanks to advances in molecular genetics and techniques to study neurotransmission, scientists have learned in studies with mice that proteins called synapsins, under the control of three genes, lock up the reserve pool by tethering its vesicles to the neuron's internal structural framework. When the cell is called upon to release extraordinary amounts of the neurotransmitter, a chemical reaction relaxes the synapsin's grasp on reserve pool vesicles, allowing them to join the releasable pool. "Although this extra mechanism is definitely not the most important action of cocaine, it points to a way that the drug can switch dopamine cells into a sustained-release mode, promoting the activation that dopamine exerts on its target neurons," says Dr. Wightman.
The Journal of Neuroscience 26(12):3206-3209, 2006. [Full Text (PDF, 90KB)]