New findings could help improve development of drugs for addiction

August 2, 2013

Scientists from the Florida campus of The Scripps Research Institute have described findings that could enable the development of more effective drugs for addiction with fewer side effects.

The study, published in the August 2, 2013 issue of the Journal of Biological Chemistry, showed in a combination of cell and animal studies that one active compound maintains a strong bias towards a single , providing insight into what future drugs could look like.

The compound examined in the study, known as 6'- guanidinonaltrindole (6'-GNTI), targets the kappa (KOR). Located on , KOR plays a role in the release of dopamine, a neurotransmitter that plays a key role in . Drugs of abuse often cause the brain to release large amounts of dopamine, flooding the brain's reward system and reinforcing the addictive cycle.

"There are a number of drug discovery efforts ongoing for KOR," said Laura Bohn, a TSRI associate professor, who led the study. "The ultimate question is how this receptor should be acted upon to achieve the best therapeutic effects. Our study identifies a marker that shows how things normally happen in live neurons—a critically important secondary test to evaluate potential compounds."

While KOR has become the focus for drug discovery efforts aimed at treating addiction and mood disorders, KOR can react to signals that originate independently from multiple biological pathways, so current drug candidates targeting KOR often produce unwanted side effects. Compounds that activate KOR can decrease the rewarding effects of abused drugs, but also induce sedation and depression.

The new findings, from studies of nerve cells in the striatum (an area of the brain involved in motor activity and higher ), reveal a point on the KOR signaling pathway that may prove to be an important indicator of whether drug candidates can produce effects similar to the natural biological effects.

"Standard screening assays can catch differences but those differences may not play out in live tissue," Bohn noted. "Essentially, we have shown an important link between cell-based screening assays and what occurs naturally in animal models."

Explore further: Study provides clues for designing new anti-addiction medications

More information: "Functional Selectivity of 6'-guanidinonaltrindole (6'-GNTI) at Kappa Opioid Receptors in Striatal Neurons," www.jbc.org/content/early/2013 … 476234.full.pdf+html

Related Stories

Study provides clues for designing new anti-addiction medications

March 22, 2012
Scientists are now one step closer to developing anti-addiction medications, thanks to new research that provides a better understanding of the properties of the only member of the opioid receptor family whose activation ...

Brain implant aims to stifle drug highs

July 29, 2013
What happens if addicts get no high from the drugs they take? Researchers at Case Western Reserve and Illinois State universities have received a $390,000 National Institute on Drug Abuse grant to help answer the question.

Research points to brain's 'dark side' as key to cocaine addiction

June 12, 2013
(Medical Xpress)—Scientists at The Scripps Research Institute (TSRI) have found evidence that an emotion-related brain region called the central amygdala—whose activity promotes feelings of malaise and unhappiness—plays ...

Receptor limits the rewarding effects of food and cocaine

July 12, 2011
(Medical Xpress) -- Researchers have long known that dopamine, a brain chemical that plays important roles in the control of normal movement, and in pleasure, reward and motivation, also plays a central role in substance ...

A path to lower-risk painkillers

June 10, 2013
For patients managing cancer and other chronic health issues, painkillers such as morphine and Vicodin are often essential for pain relief. The body's natural tendency to develop tolerance to these medications, however, often ...

Recommended for you

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.