Novel compound halts cocaine addiction and relapse behaviors

April 23, 2014 by Ellen Goldbaum
New research published by Jun-Xu Li in the UB Department of Pharmacology and Toxicology and his colleagues demonstrates that a novel compound dramatically blocked cocaine's rewarding effects and markedly blunted cocaine relapse in animals. Credit: Douglas Levere, University at Buffalo

A novel compound that targets an important brain receptor has a dramatic effect against a host of cocaine addiction behaviors, including relapse behavior, a University at Buffalo animal study has found.

The research provides strong evidence that this may be a novel lead compound for treating cocaine addiction, for which no effective medications exist.

The UB research was published as an online preview article in Neuropsychopharmacology last week.

In the study, the compound, RO5263397, severely blunted a broad range of cocaine addiction behaviors.

"This is the first systematic study to convincingly show that RO5263397 has the potential to treat cocaine addiction," said Jun-Xu Li, MD, PhD, senior author and assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences.

"Our research shows that trace amine associated receptor 1—TAAR 1— holds great promise as a novel drug target for the development of novel medications for cocaine addiction," he said.

TAAR 1 is a novel receptor in the brain that is activated by minute amounts of brain chemicals called trace amines.

The findings are especially important, Li added, since despite many years of research, there are no effective medications for treating cocaine addiction.

The compound targets TAAR 1, which is expressed in key drug reward and addiction regions of the brain. "Because TAAR 1 anatomically and neurochemically is closely related to dopamine—one of the key molecules in the brain that contributes to cocaine addiction—and is thought to be a 'brake' on dopamine activity, drugs that stimulate TAAR 1 may be able to counteract cocaine addiction," Li explained.

The UB research tested this hypothesis by using a newly developed TAAR 1 agonist RO5263397, a drug that stimulates TAAR 1 receptors, in animal models of human cocaine abuse.

One of the ways that researchers test the rewarding effects of cocaine in animals is called conditioned place preference. In this type of test, the animal's persistence in returning to, or staying at, a physical location where the drug was given, is interpreted as indicating that the drug has rewarding effects.

In the UB study, RO5263397 dramatically blocked cocaine's rewarding effects.

"When we give the rats RO5263397, they no longer perceive cocaine rewarding, suggesting that the primary effect that drives cocaine addiction in humans has been blunted," said Li.

The compound also markedly blunted cocaine relapse in the animals.

"Cocaine users often stay clean for some time, but may relapse when they re-experience cocaine or hang out in the old cocaine use environments," said Li. "We found that RO5263397 markedly blocked the effect of cocaine or cocaine-related cues for priming relapse behavior.

"Also, when we measured how hard the animals are willing to work to get an injection of cocaine, RO5263397 reduced the animals' motivation to get cocaine," said Li. "This compound makes rats less willing to work for cocaine, which led to decreased cocaine use."

The UB researchers plan to continue studying RO5263397, especially its effectiveness and mechanisms in curbing relapse to .

Explore further: Sons of cocaine-using fathers may resist addiction to drug, study suggests

Related Stories

Sons of cocaine-using fathers may resist addiction to drug, study suggests

November 11, 2013
A father's cocaine use may make his sons less sensitive to the drug and thereby more likely to resist addictive behaviors, suggests new findings from an animal study presented by Penn Medicine researchers at Neuroscience ...

Promising new drug targets for cocaine addiction found

January 20, 2014
Researchers from the Icahn School of Medicine at Mount Sinai have identified a new molecular mechanism by which cocaine alters the brain's reward circuits and causes addiction. Published online in the journal Proceedings ...

An advance in understanding drug 'habits' and their treatment

March 26, 2014
(Medical Xpress)—Cocaine promotes habitual behaviours and these can potentially be reversed with the use of an antioxidant, research at the University of Sydney has shown.

Cocaine users enjoy social interactions less

January 20, 2014
Regular cocaine users have difficulties in feeling empathy for others and they exhibit less prosocial behavior. A study at the Psychiatric Hospital of the University of Zurich now suggests that cocaine users have social deficits ...

How the brain puts the brakes on the negative impact of cocaine

January 11, 2012
Research published by Cell Press in the January 12 issue of the journal Neuron provides fascinating insight into a newly discovered brain mechanism that limits the rewarding impact of cocaine. The study describes protective ...

Resistance to cocaine addiction may be passed down from father to son, study shows

December 16, 2012
Research from the Perelman School of Medicine at the University of Pennsylvania and Massachusetts General Hospital (MGH) reveals that sons of male rats exposed to cocaine are resistant to the rewarding effects of the drug, ...

Recommended for you

Incorporating 12-step program elements improves youth substance-use disorder treatment

July 26, 2017
A treatment program for adolescents with substance-use disorder that incorporates the practices and philosophy of 12-step programs like Alcoholics Anonymous (AA) produced even better results than the current state-of-the ...

Concern with potential rise in super-potent cannabis concentrates

July 21, 2017
University of Queensland researchers are concerned the recent legalisation of medicinal cannabis in Australia may give rise to super-potent cannabis concentrates with associated harmful effects.

Findings link aldosterone with alcohol use disorder

July 18, 2017
A new study led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, demonstrates that aldosterone, a hormone produced in the adrenal glands, may contribute ...

Depression among young teens linked to cannabis use at 18

July 17, 2017
A study looking at the cumulative effects of depression in youth, found that young people with chronic or severe forms of depression were at elevated risk for developing a problem with cannabis in later adolescence.

Why does prenatal alcohol exposure increase the likelihood of addiction?

July 7, 2017
One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are ...

Researchers say U.S. policies on drugs and addiction could use a dose of neuroscience

June 23, 2017
Tens of thousands of Americans die from drug overdoses every year – around 50,000 in 2015 – and the number has been steadily climbing for at least the last decade and a half, according to the National Institute on Drug ...

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.