Researchers Create Bioengineered Mice That Resist Cocaine Addiction

A team of scientists recently used genetic engineering to create mice that are less likely to become addicted to cocaine. The mice had higher concentrations of proteins called cadherins, which can “glue” molecules together and strengthen synapses in the brain. The study, which was just published in the journal Nature Neuroscience, provides new insights into the biochemistry behind drug addiction.

When an individual uses an addictive drug, their brain chemistry is changed. Synapses, which pass signals between neurons, allow for the transfer of information throughout the brain. The strengthening of these synapses helps the brain learn and often reinforces pleasurable behaviors. Cocaine, for example, causes reward circuit synapses to strengthen. This encourages the user to take more of the drug, strengthening the synapses even more. Over time, this leads to physical addiction and a rewiring of the brain—making the habit even harder to kick.

Researchers from the University of British Columbia designed mice that had extra cadherins in their brains. Cadherins strengthen neural synapses and the team expected that these modified mice would be more prone to drug addiction. The team injected both modified and normal mice with cocaine and immediately placed them in a specific compartment of the cage. Over time, the mice began to associate a single compartment with the drug. Next, the researchers allowed the mice to roam freely in the enclosure. As expected, the normal mice became addicted to cocaine and went back to the section that had been associated with the drug. Oddly, the modified mice spent 50% less time in those compartments—showing that the extra cadherin was actually lowering the chance of addiction. After analyzing brain tissue, the team found that the additional cadherin molecules had prevented the synapses from getting stronger. In fact, the extra cadherin was blocking neurochemical receptors that are normally linked to drug addiction. The mice with more cadherin were unable to form a drug memory in the brain’s reward circuits and had no incentive to keep using cocaine.

The team’s findings were unexpected but may help physicians identify patients who may be more vulnerable to drug addiction. Substance abuse is already linked to cadherin-associated gene mutations and it’s possible that abnormally low amounts make it easier for drug memories to form. The study also provides new evidence that furthers the theory that drug addiction is a biochemical and genetic disorder, not entirely a behavioral problem.

REFERENCE

Mills et al. Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning. Nature Neuroscience (2017).

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