Heroin addiction gene identified and blocked

Jennifer Viegas

Scientists have not only identified a critical gene involved in heroin addiction relapse, but they have also successfully blocked it, eliminating cravings for the drug.

The study was conducted on heroin-addicted rats. But the researchers now think that, within a few years, better treatments will become available to human heroin users who cannot quit due to insidious cycles of relapse.

“Many people try to stop taking heroin, but in a few months almost all of them go back to using the drug,” said Ivan Diamond, at the Ernest Gallo Clinic and Research Center in California, US, and one of the research team.

David Shurtleff, director of the Division of Basic Neuroscience and Behavioral Research at the National Institute on Drug Abuse in Maryland, US, is encouraged by the research. “It will take creativity and additional research to translate this into usable therapies, but it does provide hope that we will be able to prevent compulsive drug seeking behaviour,” he told New Scientist.

Reward circuitry

Previous research has indicated that a section of the midbrain called the nucleus accumbens plays a central role in the “mental reward circuitry” of animals, such as rats and humans. This circuitry generates feelings of pleasure in response to drugs, as well as in response to other things, including food, sex and, in humans, work accomplishments.

Drugs like heroin, however, seem to over-stimulate the normal reward process to the point where users value their next fix more highly than food, water and other essentials. In 2004, a study revealed that cocaine causes a gene in the nucleus accumbens, called AGS3, to rapidly encode masses of proteins that are involved in the cravings and pleasure associated with the drug.

Diamond and his team isolated AGS3 genes and proteins in nucleus accumbens cells taken from newborn baby rats. After cloning and studying the cells in the lab, the researchers determined that AGS3’s drug-related functions are most active in the inner nucleus accumbens core as opposed to its outer shell region.

An AGS3 blocker was then created from a herpes virus. This temporarily binds to proteins within the reward circuit and blocks the cravings-pleasure cycle until the virus “washes out” of the body a few weeks later.

Eliminated desires

Heroin-addicted rats that were trained to give themselves the drug using a lever were injected with the AGS3 blocker into their nucleus accumbens after they had gone through a short period of withdrawal. A small dose of heroin then was administered to each rat.

Normally even such a tiny “taste” of the drug leads to cravings for more, but the blocker prevented the addiction relapse by eliminating these desires. The treatment produced no other observed behavioural side effects.

Diamond told New Scientist that a related treatment could become available to humans within the next couple of years. His colleague Krista McFarland, at the Medical University of South Carolina, added that one of the challenges will be to find a safe method of administering the blocker to people.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0503419102)

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