Johns Hopkins researchers have identified a compound that blocks cravings for the drug in cocaine-addicted mice.
The compound, already proven safe for humans, is undergoing further animal testing in preparation for possible clinical trials in cocaine addicts, the researchers said.
"It was remarkably serendipitous that when we learned which brain pathway cocaine acts on, we already knew of a compound, CGP3466B, that blocks that specific pathway," Solomon Snyder, M.D., a professor of neuroscience in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine, said.
"Not only did CGP3466B help confirm the details of cocaine's action, but it also may become the first drug approved to treat cocaine addiction," he said.
In the most recent study, M.D./Ph.D. student Risheng Xu worked with other members of Snyder's team to investigate whether cocaine works through the NO signaling network, and if so, how.
Using mice, they found that cocaine induces NO to react with GAPDH so that GAPDH moves into the nucleus.
At low doses of cocaine, the GAPDH in the nucleus will stimulate the neuron, but at higher doses it activates the cell's self-destruct pathway.
"This explains why cocaine can have very different effects depending on the dosage," Xu said.
The team then did experiments to see whether CGP3466B, which blocks the reaction between NO and GAPDH, would also block the effects of cocaine.
In one experiment, they placed mice in a cage with two rooms, and trained them to expect occasional doses of cocaine in one of the rooms.
When the mice began spending most of their time in that room, it showed they had become addicted to cocaine.
But when treated with CGP3466B, the mice went back to spending roughly equal amounts of time in both rooms: Their cravings had abated, Xu said.
The research is published online in the journal Neuron.