Brain-Imaging Study Offers Clues To Inhalant Abuse

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.

This work was funded by the U.S. Department of Energy, which supports basic research in a variety of scientific fields, and the National Institute on Drug Abuse. For more information on inhalants, go to: http://www.nida.nih.gov/ResearchReports/Inhalants/Inhalants.html, http://www.inhalants.org, and, for information for children, http://www.nida.nih.gov/MOM/IN/MOMIN1.html.

The U.S. Department of Energy's Brookhaven National Laboratory (http://www.bnl.gov) 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.