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January 31, 2013

Cocaine use during adolescence changes shape and size of brain regions that govern drug-seeking

Adolescents who use cocaine risk changing the part of the brain involved in reward and learning, according to research published in the January 30 edition of The Journal of Neuroscience. 

Researchers at The Hospital for Sick Children (SickKids) analyzed the effects of chronic cocaine exposure on the brains of mice. “We tracked significant interactions between the age of exposure and the drug in several brain regions that are most implicated in drug addiction,” says Dr. Paul Frankland, the Principal Investigator and a Scientist in the Department of Neurosciences & Mental Health at SickKids.

Previous research using MRI (magnetic resonance imaging) in humans has shown that cocaine use is associated with brain-structure abnormalities, but until now it has not been known if these changes are actually caused by the drug. “Our findings answer the age-old question, do young people whose brains are organized differently tend to be more vulnerable to cocaine and other drugs, or does cocaine actually alter the brain’s structure and hardware? Now we are closer to a definitive answer.”   

It is particularly important to understand the effects of drug use on the brain in adolescence because typically that is when recreational drug use starts, he adds.

Brain regions that govern drug-seeking 

The study shows that chronic cocaine use in adolescent mice altered the size and the shape of regions that are key areas for learning and memory.  “These are the areas we already know are most involved in drug addiction, governing impulse control and drug-seeking behaviour,” says study lead Dr. Anne Wheeler.

The research team used MRI to measure brain structures in both adolescent and young adult mice, and compared the animals’ brains in groups exposed to cocaine and saline. Both groups of mice were given 30 days of abstinence before regions of their brain were analyzed for shape, volume, and thickness. “The MRI gave us the precision we needed to tease apart changes throughout various brain regions, comparing the brains of drug-affected mice to the normal brains,” says Dr. Wheeler.

Brain areas that were affected include the nucleus accumbens, striatum, insular cortex, orbitofrontal cortex, ventral pallidum, substantia nigra, and medial forebrain bundle.  “When you see brain tissue in these areas that is misshaped, or too small or too large, you get an idea of why drug use is associated with loss of control of voluntary behaviour,” she says. The same effects did not occur during young-adult exposure.

Dr. Wheeler conducted the research when she was at SickKids; she is now at the Centre for Addiction and Mental Health (CAMH).

Cocaine use in both adolescent and young-adult mice also triggered changes in movement patterns, she says.

Dr. Frankland adds, “In both mice and humans, the adolescent brain is still developing. This research suggests that cocaine use by adolescents is extraordinarily risky in part because it affects brain growth in this crucial phase.” He is also Associate Professor in the Department of Physiology at University of Toronto.

Future research could investigate the structural effects of alcohol, nicotine, marijuana and other drugs on the adolescent brain, Dr. Frankland adds.  

The paper is titled “Adolescent Cocaine Exposure Causes Enduring Macroscale Changes in Mouse Brain Structure.”

The study was funded by SickKids Foundation, Canadian Institutes of Health Research, and Ontario Mental Health Foundation.  

About The Hospital for Sick Children

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.

About SickKids Centre for Research and Learning

The SickKids Centre for Research and Learning will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The facility will physically connect SickKids science, discovery and learning activities to its clinical operations.  Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The SickKids Centre for Research and Learning is funded by a grant from the Canada Foundation for Innovation, the Government of Ontario, philanthropist Peter Gilgan and community support for the ongoing fundraising campaign. For more information, please visit www.sickkidsfoundation.com/bepartofit.

For more information, please contact:

Polly Thompson
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: polly.thompson@sickkids.ca

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca