Transgenic mouse brain tissueMIKE MICHAELIDES, NIDAA popular chemogenetic technique for controlling cells does not operate in vivo in the way scientists had assumed. Reporting in Science yesterday (August 3), researchers show that CNO, a drug used in the DREADDs method (designer receptors exclusively activated by designer drugs), is not actually responsible for the effects scientists observe. Rather, it’s clozapine, a metabolite of CNO with numerous cellular targets, that binds the receptors.
These results make it imperative for researchers to do proper controls with clozapine, and indicate that they should change their protocols altogether. “I’m glad I don’t own stock in CNO,” says Scott Sternson, a neuroscientist at the Janelia Research Campus. “There’s no reason to use CNO anymore.”
Although it may be the end of CNO in these studies, coauthor Mike Michaelides of the National Institute on Drug Abuse tells The Scientist the results don’t necessarily mean the end of DREADDs. In fact, his findings might simplify things. Rather than using CNO, researchers can just administer clozapine instead because it’s the real actuator of the technique. “If they use proper controls, then hopefully it should be fine,” he says.
Clozapine was our positive control. . . ...
