Tracing the Circuits of Addiction

Learning How RNA-Modified Genes Drive Substance Abuse

The National Institute on Drug Abuse defines drug addiction as "a chronic, relapsing disorder characterized by compulsive drug seeking and use despite adverse consequences."

Still, the misconception that drug addiction is a character flaw, not a real disease, prevails. In New Mexico, one of the states with the highest rates of illegal substance use in the country, what can science tell us about the best approaches to treat and prevent drug addiction?

The answer might lie in our genes.

Nora Perrone-Bizzozero, PhD, is a professor in the UNM Department of Neurosciences with more than 20 years of experience studying the post-transcriptional mechanism controlling gene expression during brain development and maturation.

Perrone-Bizzozero is investigating the roles of microRNAs and RNA-binding proteins in drug addiction.

"Drug addiction generates an abnormal adaptation in the brain, characterized not only by acute changes in brain activity but also long-lasting changes in gene expression," she says, "so we are trying to understand the molecular mechanisms involved."

Perrone-Bizzozero teamed up with Janet L. Neisewander, PhD, an Arizona State University behavioral neuroscientist, for an RO1 NIDA grant to study microRNAs and RNA binding proteins in cocaine addiction.

They found that cocaine use drives alterations in the gene expression of the microRNA miR-495 and the RNA-binding protein HuD in the brain's reward pathway, which increases the subject's craving of the drug.

More cocaine further increases the imbalance of gene expression. These findings, published earlier this year in the journals Molecular Psychiatry and Genes, Brains and Behavior, demonstrate that microRNA and RNA-binding protein changes in the brain can affect behavior - with huge implications for understanding addiction.

After graduating from the University of Buenos Aires in her native Argentina, Perrone-Bizzozero moved to the U.S., where she started working in neuroscience and psychiatry at Harvard Medical School-affiliated McLean Hospital. She moved to Albuquerque in 1990 to join UNM.

UNM was a perfect fit for her and her husband, Oscar A. Bizzozero, PhD, chair of the Department of Cell Biology and Physiology, she says. "The environment is different than in other institutions," she explains. "Instead of competition, it promotes collaboration, both inside and outside the University."

She plans to continue deciphering the roles of non-coding RNAs and RNA-binding proteins in addiction, with an eye toward developing a cure.

"RNA-based drugs are being developed as novel treatment modalities, but they have their own challenges," she says. "It's not something that will be ready for patient care soon, but it could be a very promising approach in the future."