A genetic key to methamphetamine addiction
A mouse study has found two genes play a large role in risk for addiction to methamphetamine.
People who misuse drugs often do so partly in response to the environment they find themselves in, and partly because of their genetics. The genetic component of someone’s risk is influenced by many different genes, and most research has found that each gene has a small individual effect. A method called quantitative trait locus (QTL) analysis can help find parts of the genome that influence someone’s risk of misusing drugs. In 2013, researchers found one region on chromosome 10 in mice has a particularly large influence on how much methamphetamine an individual mouse will ingest if the drug was available in one of its two water bottles. A gene called Taar1 was particularly important in this region and another gene, called Oprm1, may also play a significant role.
When the Taar1 gene is switched off, mice consume larger amounts of methamphetamine, have a heightened reward response from the drug, and are insensitive to the adverse effects — such as hypothermia. But whether Taar1 directly caused these effects, and whether Taar1 and Oprm1 interact, had not yet been determined. If these genes played a causal role, they could be useful targets for treatment of methamphetamine-use disorder.
Stafford, Reed et al. — who include several of the researchers involved in the 2013 work — now report that when a particular variant of Taar1 was present in mice they consumed large amounts of methamphetamine. The variant codes for a faulty version of a receptor protein. When this variant was replaced with a working version using gene editing, the mice consumed less methamphetamine and also became sensitive to hypothermia induced by the drug. This confirms that this gene does play a causal role in methamphetamine consumption and hypothermia. Next, Stafford, Reed et al. tested mice with different combinations of variants of Oprm1 and Taar1 to see how the genes interacted. The results showed that the effects of Taar1 on both consumption of the drug and hypothermia depended on the Oprm1 variant present.
The findings suggest that variants of these two genes in humans could influence an individual’s risk of addiction to methamphetamine. It is possible that in future the disorder could be treated by drugs that modify the brain activity impacted by these receptors. But first, it will be important to find out if these genes play a similar role in humans as they do in mice.
Originally published at https://elifesciences.org/digests/46472.
