Team discovers possible ’universal strategy’ to combat addiction

An international research team led by the University of Saskatchewan has discovered a signaling pathway in the brain involved in drug addiction, together with a method for blocking its action, that may point to a single treatment strategy for most addictions. Their findings appear in the March issue of the prestigious journal Nature Medicine.

The team, led by Xia Zhang, associate professor in the U of S department of psychiatry, found that a naturally occurring enzyme known as PTEN acts on the part of the brain where many drugs of abuse exert their rewarding effects – the ventral tegmental area (VTA).

“Our results suggest a potential universal strategy for treating drug addiction,” Zhang says. “Most drugs of abuse act on the neurons in this area.”

He cautions that much work remains to be done before a treatment based on the discovery could be developed to help drug addicts. This includes several years of further testing, including animal and, finally, human trials.

“We have our peptide, but there’s a long way to go before a clinical application,” he says.

“Dr. Zhang’s research is important to our understanding of drug addiction. His work epitomizes how health research holds the key to improved health and quality of life for Canadians and people throughout the world,” said Dr. Rémi Quirion, Scientific Director of the Canadian Institutes of Health Research Institute of Neurosciences, Mental Health and Addiction.

Zhang, who worked with colleagues at the U of S, University of Toronto, and Vanderbilt University in Tennessee on the project, explains that VTA brain cells are sensitive to serotonin, a hormone associated with learning, sleep and mood. The team discovered that PTEN acts on these serotonin receptors, increasing brain cell activity. This is the same “reward” process sparked by drugs of abuse.

Armed with this knowledge, the team designed a molecule called a peptide, tailored to fit the serotonin receptors and block PTEN. When rats were treated with this PTEN-blocker, it shut down the drug reward process – including the process that induces craving and withdrawal.

The study, funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council, looked at nicotine and THC (the active ingredient in marijuana). However, Zhang says the results could also hold true for other drugs such as cocaine, heroin, and even methamphetamine.

Zhang’s U of S research team is part of the Neural Systems and Plasticity Research Group, one of several interdisciplinary health sciences research groups at the University.

The group, dedicated to the study of brain systems and how they change with experience, draws expertise from numerous departments across six colleges on campus.