Science: Chilean Researchers Discover Drug-Craving Brain Region in Rats

Rats prefer the dark compartment in a place preference apparatus, but amphetamine-addicted rats will leave the dark when it craves drugs and go to the brightly lit area where it has been administered amphetamines. When researchers blocked the insula and the rat no longer craved the drugs, the rat returned to the dark compartment.
[Image © Science]

SANTIAGO, Chile—Chilean researchers have identified a region of the brain—the insular cortex—that plays a role in drug craving in amphetamine-addicted rats, according to a report published in the 26 October issue of the journal Science.

This finding ultimately may help support the development of new therapies to treat drug addiction as well as certain behavioral side effects of medications, the authors said in an interview.

The insular cortex, also known as the insula, lies deep inside the brain. It is a part of the interoceptive sensory system that monitors the body's perception of its physiological states and needs.

The researchers used rats for these studies and before the findings can be shown to apply in humans, researchers will have to perform similar tests in human subjects.

"Our finding that blocking the insula prevents the craving for amphetamine in amphetamine-dependent rats indicates to us that this region of the brain processes information about the physiological states of the body and may guide behavior," explained researcher Fernando Torrealba of the Pontifical Catholic University of Chile.

Torrealba, along with lead author Marcos Contreras and Francisco Ceric, presented their research at the first ever Science press conference in Chile. The 25 October event, held in Spanish, was widely attended, with reporters from the two leading Chilean newspapers, El Mercurio and La Tercera, as well as the popular Channel 13 television station and the global Reuters news wire.

Drug addicts become irritable and anxious when the body craves the drug. Working with amphetamine-addicted rats, the scientists first inactivated the insular cortex by injecting a drug that temporarily silenced all neuronal activity in this area.

This male rat spends a lot of time in the white compartment, in spite that this too illuminated room makes it anxious. This rat is craving for amphetamine, and is prepared to overcome its natural aversion of illuminated spaces to get an amphetamine injection while in the white compartment.
[Image © Science]

After the injection, the addicted rats did not seek amphetamines and returned to their normal behavior—specifically, preferring a darkened compartment rather than a bright white region of an experimental apparatus. When the blocking was reversed, the rats once again showed signs of craving amphetamines, preferring the white compartment.

In a second experiment, the researchers injected rats with lithium, which is a drug used to treat mood disorders; the drug also can cause gastrointestinal discomfort and malaise. Rats "quickly laid on their bellies," showing signs of malaise, according to the Science paper. When researchers inactivated the insula before administering lithium, however, the rats no longer exhibited signs of discomfort and appeared to behave normally.

"This showed us that the insular cortex not only informs the rest of the brain about craving, but also the signs of gastrointestinal discomfort, and that this information about bodily states may guide behavior," Torrealba said. "Since this region serves the perception of bodily needs and emotions, it may be a key structure in decision-making by informing the executive prefrontal cortex of our needs as in the case of drug abuse."

While long-term lithium use is known to cause malaise in human patients, the lithium test was not meant to mimic the chronic therapy for mood disorders among people.

"This study is significant, not only for its practical and therapeutic implications for the development of future treatments for drug addiction, but also from a basic science point of view because it gives new insights into the function of the insular cortex," said Peter Stern, a senior editor for Science.

Torrealba and colleagues plan to continue their research to see if they can prevent craving for longer time periods and want to investigate if they can alleviate other distressful systems.

Evelyn Brown

26 October 2007