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Study Involving Heroin-Addicted Rats Expose Relapse Gene

Through studying heroin-addicted rats, researchers have identified genes that may be involved in drug relapse. Science Daily reports that Kara Kuntz-Melcavage, from Pennsylvania State University College of Medicine, and a team of researchers found a group of genes in the rats whose expression is significantly altered following being exposed to drug paraphernalia after an enforced “cold-turkey” period.

“A number of gene expression studies have investigated changes induced by drug exposure, but few reports describe changes associated with the mental state that leads to relapse. We identified 66 genes involved in the relapse response, including some that are important for neuroplasticity, and through that role may impact learning and behavior,” said Kuntz-Melcavage.

The researchers attached rats to a drug supply that for 3 hours each day delivered heroin into their jugular veins when they licked a particular empty spout. Over a two-week period, the animals were free to self-administer heroin, while control rats to whom they were linked received saline instead.

One group of addicted rats and their non-addicted partners were then kept without heroin for two weeks before being re-exposed to the spout, which no longer yielded drug infusions. After 90 minutes in this narcotic-associated environment, during which the addicted rats compulsively returned to lick the unrewarding empty spout, they and their control mates were humanely killed and gene expression in their brains was studied.

By comparing the gene expression in the drug-seeking animals with that in a second group of addicted rats re-exposed to the narcotic environment after only one day of abstinence, and with the controls which were given saline, the researchers were able to identify genes involved in relapse behavior.

“The session with the inactive spout served not only to provide an opportunity to observe drug-seeking behavior, but also mimicked a real-life situation in which environmental cues precipitate relapse behavior following an extended period of abstinence,” said Kuntz-Melcavage.

She added, “As data accumulate, the existence of a single ‘relapse gene’ is looking increasingly unlikely–it is likely to be a constellation of different genes. Therefore, large scale views of gene expression, like this one, will prove very useful for guiding research into human drug-associated behavior.”

Recovery is Harder For Addicts Who Start Young

A NIDA-funded study has demonstrated that the relapse rate for heroin addicts increases with time and that the probability of long-run abstinence depends on the age of first drug use. Those who start daily heroin use at a younger age are more likely to relapse than those who start later.

The study, conducted by Dr. Marnik G. Dekimpe of the Catholic University Leuven in Belgium and his colleagues in Belgium and at the University of California, Los Angeles, examined the treatment histories of 846 patients at methadone clinics in central and southern California. The researchers looked at males and females, whites and Chicanos, most of whom started using heroin between the ages of 17 and 25. Subjects were interviewed over a 4-year period during and after treatment to determine the probability of their relapse to heroin use.

The finding that relapse is connected to time suggests the need for long-term periodic monitoring of a former heroin user’s abstinence, Dr. Dekimpe says. The researchers also found drug relapse odds were significantly different across the socio-demographic groups studied, suggesting that prevention resources could be directed to groups at higher risk. No significant differences in relapse probability were associated with either gender or education.