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Brain-imaging study offers clues to inhalant abuse—huffing



These baboon brain scans show where toluene, a common solvent, goes in the brain two minutes after it was injected into the animals. The red end of the scale indicates the highest concentration. The image on the left shows that toluene quickly enters the brain's striatal region (arrows), the area directly associated with reward and pleasure. The image on the right shows toluene entering deep cerebellar nuclei, the brain region involved in voluntary movement. These findings are in agreement with clinical evidence that toluene abusers ("huffers") experience a rapid "high," and also suffer neurological symptoms such as ataxia (lack of coordination) and slurred speech.

First images of inhalants in the brain reveal why solvents may be so addictive, in a Department of Energy Brookhaven National Laboratory study, which will appear in the April 26 issue of the journal Life Sciences.

April 22, 2002—Inhalant abuse, also known as "huffing," is a rapidly growing health problem, particularly among young people. However, little is known about how inhaled chemicals affect the brain and body. Now, scientists at the Brookhaven National Laboratory—inspired by schoolchildren who wanted to know more about huffing—have produced the first-ever images showing what parts of the brain and body are most affected by toluene, a commonly inhaled solvent. The study, which was performed in baboons and mice, appears in the April 26 issue of the journal Life Sciences (available online April 15).

The images show that toluene moves into the brain rapidly and initially affects the same brain regions as cocaine and other abused drugs. Then, toluene spreads more generally to the entire brain before clearing the body rapidly via the kidneys.

"This affinity for brain regions associated with reward and pleasure, as well as the quick uptake and clearance, may help to explain why inhalants are so commonly abused," said lead author Madina Gerasimov, a Brookhaven chemist.

"For the first time, we have shown in living animals where the most commonly used solvent goes in the brain and the whole body," said Brookhaven neuroanatomist Stephen Dewey, a coauthor.

"This study was really born out of my going to elementary schools, where I've been giving talks about Brookhaven's addiction research since 1995," said Dewey. During his talks, children as young as fourth and fifth graders would sometimes ask him about huffing. "After about the third or fourth time someone asked me, I proposed that we develop a way to label and image solvents, which seem to be a 'gateway' drug of abuse for some young children," he said.

The team chose toluene because it is one of the most common industrial solvents, found in paints, glues, and other household products often abused by huffers. To label the toluene, Brookhaven chemists replaced some of the compound's carbon atoms with a radioactive isotope, carbon-11. This radiolabeled toluene was then injected into the experimental animals. (The scientists used injection rather than inhalation as an administration route so that they would know precisely how much toluene the animals were given.)

The level of the radioisotope was then measured using a positron emission tomography (PET) camera, which picks up the radioactive signal, shows exactly where the toluene is located in the body, and tracks its location over time. Other tissue-sampling methods were used to track the toluene as well.

The scientists were surprised by the findings. "I couldn't believe it," Dewey said. "The theory has always been that the effects of solvents would not be very specific—that if you breathe them in they'd go everywhere equally," he said. "But, in fact, it looks like there's a regional distribution. They go to specific regions associated with reward and pleasure, just like other abused drugs. Then over time, they redistribute."

The initial specificity for the brain's reward centers may help to explain the addictive potential of inhalants, while the redistribution to the entire brain seems to mirror clinical changes observed in huffers. Unlike other drug abusers, who have damage in the reward centers, Dewey explained, "huffers have a much more global disease," with changes in areas of the brain that may interrupt normal learning and memory more quickly than other drugs.

In addition to offering insight into the nature and effects of inhalant abuse, Gerasimov said this study is also a technical advance in radiochemistry. "It's the first time chemists have labeled and purified a solvent for imaging," she said. This may open up a whole new field of study into the effects of a wide array of solvents found in common, everyday products from cleaning fluids to hairsprays.

"There isn't a person among us who isn't exposed to solvents," Dewey said.

The Brookhaven team is already applying for grants to study other inhalants, first in animals and then in humans. They are also working to develop a method to study these chemicals in inhaled as well as injected form to further their understanding of the mechanisms.—by Karen McNulty Walsh

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Media contacts: Karen McNulty Walsh, Brookhaven National Laboratory, (631) 344-8350, kmcnulty@bnl.gov
Mona S. Rowe, Brookhaven National Laboratory, (631) 344-5056, mrowe@bnl.gov
Technical contacts: Stephen Dewey, Brookhaven National Laboratory, sld@bnl.gov
Madina Gerasimov, Brookhaven, National Laboratory, madina@bnl.gov

Related Web Links

For Parents: "What Every Parent Should Know About Inhalent Abuse," by Stephen Dewey, Brookhaven National Laboratory (PDF)

For Children: "The Brain's Response to Inhalants," Mind Over Matter (MOM), National Insitute on Drug Abuse, National Institutes of Health.

Fact Sheet: Inhalent Abuse: A Growing Public Health Problem (PDF)

Report: "Inhalent Abuse," National Institute on Drug Abuse Research Report Series

Funding: This work was funded by the U.S. Department of Energy's Office of Biological and Environmental Research within the Office of Science, and the National Institute on Drug Abuse within the National Institutes of Health.

Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies. Brookhaven also builds and operates major facilities available to university, industrial, and government scientists. The Laboratory is managed by Brookhaven Science Associates, a limited liability company founded by Stony Brook University and Battelle, a nonprofit applied science and technology organization.

Author: Karen McNulty Walsh, a Senior Public Affairs Representative at Brookhaven National Laboratory since September 1999, has an MA in science journalism from New York University and a BA in biology from Vassar College. She was previously the editor of Science World, a science magazine for middle-school children, and Zillions, a kids' version of Consumer Reports. For more science news, see see Brookhaven's Laboratory News.

 

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