Drug Has Potential to Prevent Alcoholics From Relapsing

07/23/08  Portland, Ore.

OHSU scientist identifies brain receptor that triggers euphoric feelings from alcohol as well as a drug that blocks the heightened pleasure alcoholics experience when they resume drinking

An experimental drug that blocks the euphoric feelings associated with drinking may prevent alcoholics from relapsing. The finding, the result of a mouse study at Oregon Health & Science University, could lead to human clinical trials within the next year.

“We showed we could block behavior in mice that resembles this increased euphoria even after the animals had been given a lot of alcohol,” said Tamara Phillips, Ph.D., professor and vice chair of the behavioral neuroscience department at OHSU and a research scientist at the Portland Veterans Affairs Medical Center. “That’s what you want in a treatment, because we don’t get to people until after they become addicted to alcohol.”

Earlier research has shown that some people’s brains become sensitized as a result of chronic exposure to alcohol. This change in the brain does not subside after people quit drinking. So when they begin consuming alcohol again, “they get a bigger jolt,” Phillips said.

Alcohol consumption causes the body to release a substance known as “corticotrophin-releasing factor” or CRF. It activates receptors in the brain. Phillips and her team determined that a brain receptor called CRF1 appears to be involved in this heightened pleasure sensation. They compared the responses of normal mice and mice bred without the CRF1 receptor to chronic doses of alcohol
.Mice without the CRF1 receptor did not experience the euphoric jolt the normal mice demonstrated.

The research team also took normal mice with the CRF1 receptor and exposed them to chronic doses of alcohol. Before testing for the euphoric response, the researchers gave the mice an experimental drug called CP 154,526 - developed by Pfizer - which prevents CRF from reaching the brain receptor. This group of mice also did not experience the heightened reaction.

Phillips’ study recently was published in the Proceedings of the National Academy of the Sciences.The results may be particularly applicable to stress-induced relapse. That’s because the CRF1 receptor also triggers the body’s response to stress.

This could have implications for PTSD patients. “I think if you block this receptor, you might be able to decrease drinking in response to PTSD,” Phillips said.

The next step is testing CP 154,526 to see if it is safe for use in humans. If it clears that hurdle, researchers will start human trials to determine if the drug can prevent alcoholic relapse.





About OHSU
Oregon Health & Science University is the state’s only health and research university, and Oregon’s only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,400 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.

As a leader in research, OHSU earned $307 million in research funding in fiscal year 2007. OHSU serves as a catalyst for the region's bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every three days, with more than 4,100 research projects currently under way. OHSU disclosed 132 inventions in 2007 alone, and OHSU research resulted in 33 new spinoff companies since 2000, most of which are based in Oregon.