Discovery may lead to cure for drug addiction

March 22, 2011
Green SNX27

SNX27 proteins (shown in green) in the hippocampus, the brain's learning and memory center (Image credit: Kalyn Stern and Paul Slesinger)

Biologists at the Salk Institute for Biological Studies have deciphered a molecular code that regulates availability of a brain channel that modulates neuronal excitability, a discovery that might aid efforts to treat drug addiction and mental disorders, says Paul Slesinger, Ph.D and colleagues.

The study showed that a regulatory factor called SNX27 targets a brain channel protein called GIRK (G-protein-coupled inwardly rectifying potassium channels) for destruction.

SNX27 PDZ

SNX27 proteins reside in neurons below GIRK channels (Image: Bartosz Balana and Paul Slesinger)

Slesinger and others have shown that alcohol or club drugs (such as GHB) linked to sexual assault¬† affect GIRK channel function in the brain. Loss-of-inhibition behaviors associated with abuse of these substances result from the fact that GIRK channels allow potassium ions to leak out of a stimulated neuron, thereby dampening a cell’s excitability.

Slesinger’s team confirmed that SNX27 resides in neurons, just below the membrane where active GIRK channels sit. They showed that cells were less responsive to drugs that activate channels, suggesting that SNX27 waylays membrane-bound GIRKs and blocks their function.

SNX27 levels reportedly increase in rodent models of addiction to stimulants like cocaine and methamphetamine. Selectively blocking this newly identified interaction between GIRK and SNX27 might thwart addiction, suggests Slesinger.

Their work appears in the online early edition of the Proceedings of the National Academy of Sciences.