Brain and Body

Researchers Discover New Potential to Block Compulsive Drug-Seeking Behavior

August 11, 2016 | Kelly Tatera

Girl sniffing cocaine
Photo credit: andronicusmax/flickr (CC BY 2.0)

In a study with cocaine-addicted mice. 

According to a new study by scientists at The Scripps Research Institute (TSRI), higher levels of a molecule located in the brain, called hypocretin, may be involved in cocaine addiction.

"Cocaine addiction is a disorder that affects millions of people worldwide," study co-author Marisa Roberto, a professor in TSRI's Committee on the Neurobiology of Addictive Disorders (CNAD), said in a press release. "Understanding the mechanisms underlying cocaine addiction is important for identifying potential new targets for therapeutic use.”

Hypocretin plays a key role in a brain network, called the hypothalamic hypocretin/orexin system (HRCT), which sends signals between brain regions. It’s also known to influence the brain’s reactions to certain drugs, like cocaine, alcohol, nicotine, and opioids, as well as an individual’s desire to relapse.

In order to better understand hypocretin’s role in addiction, the team focused on changes in the central amygdala, which is a brain region linked with stress and negative emotions during drug withdrawal.

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Rats were split into two groups: one was given the option to self-administer cocaine for an hour a day, and the other had the option to self-administer cocaine for six hours a day. The first group was designed to mimic the conditions of short-term, occasional drug use, while the second mimicked compulsive drug use and addiction.

According to the results, which appear in the journal Biological Psychiatry, the researchers found that compulsive cocaine use triggers the HRCT system in such a way that further drug-seeking is motivated.

In particular, the central amygdala becomes overactive due to increased levels of hypocretin. The researchers say that this overactivity is linked to the anxious state in rats that seems to urge them to continue seeking out cocaine.

"The rats escalate their daily intake as many human users would," said Roberto.

With these findings in mind, the researchers decided to see how the rats would react if HCRT activity was blocked. The animals were given an antagonist to block activity at one of the two HCRT receptors in the brain, and excitingly, the drug-seeking behavior was reduced.

This suggests that blocking hypocretin may pave the way to a new treatment for addiction and relapse.

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