Molecular connector helps cocaine latch on to brain cells, even when drug is in low doses: Study in mice shows that the BASP1 connector molecule may also underlie gender differences in cocaines effects

Scientists have long known that cocaine works by latching on to molecular connectors on the surface of brain cells, allowing dopamine, a chemical that promotes feelings of pleasure and reward, to accumulate in the space between brain cells. Now, Johns Hopkins Medicine scientists say they have found a molecular connector, known as the BASP1 receptor, that binds cocaine, even when the drug is present in very low doses.

The study, conducted in mice and laboratory-grown mouse brain cells, suggests that blocking the BASP1 receptor may reduce the stimulant effect of cocaine, but only in male mice, not in females, maybe due to the stronger presence of estrogen hormone in the females.

A report on the research was published in the April 19 issue of the Proceedings of the National Academy of Sciences.

Experts have long concluded that cocaine essentially acts as a plug, connecting to brain cells via a molecular “receptor,” and stopping brain cells from sucking in dopamine chemicals through a strawlike structure called a transporter. All of this happens in the space where two brain cells meet and trade chemicals — a synapse. When dopamine fills up a synapse and isn’t absorbed by brain cells, feelings of reward and pleasure last longer.

Scientists have already identified several such transporters and receptors associated with cocaine, but all of them require moderate to high doses of cocaine to effectively link. The Johns Hopkins Medicine team, led by the study’s first author, Maged Harraz, M.B.B. Ch., M.Sc., Ph.D., aimed to find a receptor capable of binding cocaine at low doses. Harraz is an instructor of neuroscience at the Johns Hopkins University School of Medicine.

To do that, Harraz and his colleagues first added cocaine to mouse brain cells in laboratory culture dishes. Then, he ground down the cells, looking for molecules that bound to cocaine. At a concentration of 7 nanomolar of cocaine, an amount that does not engage any known receptor for cocaine, Harraz found the drug bound to the BASP1 receptor.

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