Cocaine and the Teen Brain: New Insights Into Addiction

When first exposed to cocaine, the adolescent brain launches a strong defensive reaction designed to minimize the drug's effects, Yale and other scientists have found. Now two new studies by a Yale team identify key genes that regulate this response and show that interfering with this reaction dramatically increases a mouse's sensitivity to cocaine. 

The findings may help explain why risk of drug abuse and addiction increase so dramatically when cocaine use begins during teenage years. 

The results were published in the Feb. 14 and Feb. 21 issues of the Journal of Neuroscience. 

Researchers including those at Yale have shown that vulnerability to cocaine is much higher in adolescence, when the brain is shifting from an explosive and plastic growth phase to more settled and refined neural connections characteristic of adults. Past studies at Yale have shown that the neurons and their synaptic connections in adolescence change shape when first exposed to cocaine through molecular pathway regulated by the gene integrin beta1, which is crucial to the development of the nervous system of vertebrates. 

"This suggests that these structural changes observed are probably protective of the neurocircuitry, an effort of the neuron to protect itself when first exposed to cocaine," said Anthony Koleske, professor of molecular biophysics and biochemistry and of neurobiology and senior author of both papers. 

In the latest study, Yale researchers report when they knocked out this pathway, mice needed approximately three times less cocaine to induce behavioral changes than mice with an intact pathway. 

The research suggests that the relative strength of the integrin beta1 pathway among individuals may explain why some cocaine users end up addicted to the drug while others escape its worst effects, Koleske theorized. 

"If you were to become totally desensitized to cocaine, there is no reason to seek the drug," he said. 

Koleske and Jane R. Taylor, professor of psychiatry and psychology and an author of the Feb. 14 paper, are teaming up with other Yale researchers to look for other genes that may play a role in protecting the brain from effects of cocaine and other drugs of abuse. 

Shannon Gourley, now of Emory University who worked with Koleske and Taylor, is lead author on the Feb. 14 paper detailing how the structural response to cocaine protects against cocaine sensitivity. Anastasia Oleveska and Michael S. Warren are other Yale authors on this paper. Warren and William D. Bradley of Yale are co-lead authors of the latest Neuroscience paper describing the role for integrin beta 1 in the control of adolescent synapse and dendrite refinement and stability. Yu-Chih Lin, Mark A. Simpson, Charles A. Greer are other Yale-affiliated authors. 

Author: Bill Hathaway | Source: Yale University [February 21, 2012]

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Erasing The ‘Memory’ Of Cocaine: A Breakthrough In Treating Addiction

Unlike many other drugs, cocaine does not trigger a physical addiction. It can however cause a psychological one in some 20% of its users, which can push them to lose control over their consumption, and can often lead to dire consequences. 

Hooked on the memory [Credit: andronicusmax]

It is also that psychological addiction that lasts even after rehab, because the brain will forever remember having taken the drug  

Now, neuroscience researchers from Geneva University may have found a way to erase that memory through a new laser technique that they have successfully tested on mice. 

The scientists focused on a part of the nervous system called the “reward circuit.” The main function of this network of brain cells is associating vital behaviors – like eating or reproducing – with feelings of pleasure. Information is transmitted between two different areas of the brain: one holds information on levels of satisfaction, and the other registers the context in which it happened. 

Cocaine abnormally raises levels in the brain of dopamine, a substance responsible for the transmission of information between both parts of the brain. That phenomenon forever marks the brain and explains why even after years of sobriety, a recovering addict can still be tempted by the drug. 

“Take someone who took cocaine in a certain place. Even sober, this person won’t be able to walk by that same place without some of his brain cells getting excited and awakening a desire to take the drug,” says Vincent Pascoli, the lead researcher. 

It is this hidden memory, mixing context and desire to use, that the researchers say can be erased. Working on mice that have ingested cocaine, they infect certain brain cells in a virus that introduces a light-sensitive protein that can be targeted by a laser. With the use of a laser, researchers were able to control brain activity and bring information transmission levels back to normal. 

The process proved a success in the short term, with the mice acting like they’d never taken cocaine in the days following the procedure. The long-term effects have yet to be tested on mice. And of course, the procedure must still be tried on humans. 

Source: Le Temps vya Worldcrunch [December 14, 2011]

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