By On January 24th, 2019

New treatment could reduce relapse risk after cocaine addiction

New research from scientists at the University of Pittsburgh may have revealed a powerful target for treating cocaine addiction and prevention relapse.

Not only did the team of researchers establish a clear relationship between heightened synapses in circuits linking two regions of the brain with cocaine use, but they were able to also show that weakening this circuit could reduce relapse rates in animal tests.

As the researchers report in the journal Cell Reports, the circuit linking the medial geniculate nucleus (MGN) in the thalamus and the lateral amygdala (LA) strengthen with cocaine use and reinforce memories that link the “highs” with environmental triggers.

Notably, the medial geniculate nucleus helps process sensory stimulation such as sounds or visual information, while the lateral amygdala processes reward and motivation.

After this, the team used two methods to weaken the MGN-LA circuit synapses and thus weaken or “erase” the link between cocaine-related memories and environmental triggers. When tested in mice, the animals showed significantly lower drug-seeking behavior on exposure to environmental stimulus compared to non-treated mice.

The first method used an indirect approach utilizing exposure therapy to modify the brain behaviors related to environmental information. The other, however, directly weakened the synapses using optogenetics to reduce cell function.

While both methods effectively reduced drug-seeking behavior by seemingly disrupting the memories linked to environmental stimulus, the report shows that the direct modification to cell performance was more effective at reducing relapse rates even when the mice were tested in different environments.

“While we’ve always known that the brain forms these cue-associated memories,” says senior study author Mary M. Torregrossa, Ph.D., “the specific circuits have never been clearly identified.

Torregrossa is an associate professor of psychiatry at the University of Pittsburgh.

Exposure therapy is a widely-used treatment strategy for a number of mental health issues, including addiction, phobia, and post-traumatic stress disorder. It works by using a number of specific approaches to sever the tie between specific environmental cues and memories.

However, exposure therapy’s effectivity when treating drug addiction has been inconsistent at best. While it appears to succeed while patients are in controlled environments, the risk of relapse often remains high once they re-enter the world.

Using optogenetics, the researchers appear to have found a solution to the issue. By directly manipulating the cells to reduce synapse expression, the researchers were able to significantly reduce relapse rates in the mice even when placed into new environments.

“In the long-term,” concludes Torregrossa, “these findings may help us develop drugs or approaches like deep brain stimulation to specifically target these memories strengthened by substance use and improve the success of exposure therapy to prevent relapse.”

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