NIDA research published January 17 in Cell provides insight into the mechanism of action of the Sigma-1 receptor (Sig-1R), a protein located inside brain nerve cells that has long been suspected of contributing to the persistent, harmful effects of chronic cocaine use. The mouse study showed that cocaine caused Sig-1R to move from the inside of a neuron to its surface. This major molecular relocation resulted in increased interaction between Sig-1R and Kv1.2 -- a potassium channel protein -- in the nucleus accumbens, a region of the brain linked to reward processing. Because potassium channels decrease neuronal excitability, increased Sig-1R/Kv1.2 interactions in the nucleus accumbens could result in enhanced responsiveness to cocaine (behavioral sensitization). Such increased rewarding properties of cocaine could contribute to the development of addiction.
The study, co-authored by NIDA Scientific Director Dr. Antonello Bonci, could mark the beginning of new discoveries that bring us closer to discovering novel medications for addiction and other neurodegenerative or psychiatric disorders.
For a copy of the study abstract, go to http://www.cell.com/abstract/S0092-8674%2812%2901491-2. For more information on NIDA’s Intramural Research Program, go to http://irp.drugabuse.gov/.
For more information, contact the NIDA press office at media@nida.nih.gov or 301-443-6245.