Novel drug targets for treatment of alcohol abuse
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Alcohol abuse is a worldwide health problem that creates a tremendous burden for society, families of affected individuals, and the healthcare system. In the US, about 3% of adults abuse alcoholic beverages and develop behavioral patterns of alcoholism. Total cost of alcohol abuse to society is estimated at $ 180 billion per year. While educational programs aim at prevention during early stages of alcohol consumption, little therapeutic opportunities exist for established alcohol abusers. Only three drugs are currently approved by the FDA for the treatment of alcohol abuse, each having either limited effectiveness or low compliance. Since alcohol has powerful reinforcing effects that promote formation of strong reward memories, abstinent ex-abusers are under constant threat of relapse. In fact, within 6 months after alcohol detoxification, relapse rates increase to almost 50%. Therefore, new supporting pharmacotherapies are urgently needed to help maintain abstinence. Previous research by the UC Irvine lab and other groups has found evidence that a newly discovered transmitter system in the brain, termed Neuropeptide S (NPS), can trigger relapse to alcohol-seeking behavior in animal models. Conversely, preliminary experiments suggest that blocking NPS signaling might prevent reinstatement of drug-seeking behaviors. The NPS system might interact with specific brain reward systems to produce these effects. Therefore, the current proposal aims at increasing knowledge about NPS and its potential for development of novel drugs to treat relapse of alcohol-seeking behavior. For this purpose, we plan to use an animal model of alcoholism in which mice first learn to self-administer alcohol, followed by detoxification, and then investigate if blocking the NPS system can prevent reinstatement. The studies will also measure changes in brain chemicals that are associated with the rewarding effects of alcohol. A mouse model in which NPS signaling has been genetically inactivated will be used to test whether such mice are less susceptible to reinstatement of alcohol-seeking behavior. It is expected that the results of this project will validate the NPS system as a promising target for development of drugs to prevent relapse into alcohol-seeking behavior. We, in collaboration with Johnson &amp; Johnson Pharmaceutical Research &amp; Development, L.L.C. San Diego, will bring together cutting edge basic and applied research with a clear perspective for developing new therapies for alcoholism. Successful completion of the project could justify the launch of a larger drug discovery program. Such a program could bring substantial resources to California, help to stabilize existing positions in biomedical research and create new jobs. The current proposal will also train graduate students in state-of-the-art technology. Finally, development of more efficacious treatments for alcoholism could be a benefit to society, especially for patients and their closest acquaintances.