Second Mechanism in Cocaine Addiction

A research team has found a mechanism in the brain that is key to making cocaine seem pleasurable, which could lead researchers to finding drug treatment for addiction, Science Daily reports. Led by the University of Colorado Boulder and assisted by scientists at University of Adelaide in Australia and the National Institute on Drug Abuse, researchers discovered that cocaine's impact on neurons does not fully explain the drug's dramatic effects on reward.

The effect of cocaine works by increasing the amount of dopamine in the brain, a neurochemical associated with feelings of pleasure and blocking the ability for the brain to reabsorb the dopamine. The temporary blocking of dopamine reabsorption is what makes the user feel euphoric for an extended period of time.

The researchers' focus in this study was on a second mechanism in the brain which may contribute to the abuse potential of cocaine. They found that the second mechanism centers on glial cells, an important component of the brain's immune system. Researchers found that cocaine binds to glial cells which then triggers an inflammatory response in the TLR4 area of the brain, exciting neurons and further increasing the amount of dopamine released in the brain.

"We've demonstrated conclusively that cocaine interacts with TLR4 to produce a pro-inflammatory effect in the brain," said Alexis Northcutt, a CU-Boulder research associate in the Department of Psychology and Neuroscience and lead author of the paper. "The effect is necessary to convey the drug's rewarding effects. Without it, reward is greatly reduced."

Previous research has found that using the drug (+)-naltrexone inhibits opioids from binding to TLR4, according to the article.

"We found the same results when studying cocaine, which means the same drug, (+)-naltrexone, might be useful for treating a wider range of drug addictions," said senior author CU-Boulder Professor Linda Watkins. "The exciting news is that this drug is already in development by Xalud Therapeutics."

The findings were published in Nature journal Molecular Psychiatry.