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    BNL Brain-Imaging Study Offers Clues to Inhalant Abuse

    Scientists at the U.S. Department of Energy’#146;s Brookhaven National Laboratory(BNL) have produced the first-ever images illustrating the parts of the brainand body associated with the abuse of inhalants, also known as huffing. Theresearch reveals why solvents may be so addictive, pointing to the famous pleasureand reward circuit of the brain. The study, which was performed in baboons andmice, appears in the April 26 issue of the journal Life Sciences.

    Inhalant abuse is a rapidly growing health problem, particularly among youngpeople. Inspired by curious schoolchildren, BNL scientists expanded their intereststo include the possible implications of huffing.

    ‘This study was really born out of my going to elementary schools, whereI’#146;ve been giving talks about Brookhaven’#146;s addiction research since1995,’ said BNL neuro-anatomist Stephen Dewey, a coauthor on the study.

    During his talks, children as young as fourth and fifth graders would sometimesask him about huffing.

    ‘After about the third or fourth time someone asked me, I proposed thatwe develop a way to label and image solvents, which seem to be a ‘#145;gateway’#146;drug of abuse for some young children,’ he said.

    The research team chose to study toluene because it is one of the most commonindustrial solvents, found in paints, glues, and other household products oftenabused by huffers.

    To label the toluene, BNL chemists replaced some of the compound’#146;s carbonatoms with a radioactive isotope, carbon-11. This radio-labeled toluene wasthen injected into the experimental animals. (The scientists used injectionrather than inhalation as an administration route so that they would know preciselyhow 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 thetoluene is located in the body, and tracks its location over time.

    ‘For the first time, we have shown in living animals where the most commonlyused solvent goes in the brain and the whole body,’ Dewey said.

    The images show that toluene moves into the brain rapidly and initially affectsthe same brain regions as cocaine and other abused drugs.

    Then, toluene spreads more generally to the entire brain before clearing thebody quickly 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 inhalantsare so commonly abused,’ said lead author Madina Gerasimov, a BNL chemist.

    The scientists were surprised by the findings, which appeared to contradictthe previously accepted mechanism of solvent effects.

    ‘The theory has always been that the effects of solvents would not bevery specific ‘#151; that if you breathe them in they’#146;d go everywhere equally,’Dewey said. ‘But, in fact, it looks like there’#146;s a regional distribution.They go to specific regions associated with reward and pleasure, just like otherabused drugs. Then over time, they redistribute.’

    The initial specificity for the brain’#146;s reward centers may explain theaddictive potential of inhalants, while the redistribution to the entire brainseems to mirror clinical changes observed in huffers. Unlike other drug abuserswho have damage in the reward centers, Dewey explained that ‘huffers havea much more global disease.’ The damage occurs in areas of the brain thatmay interrupt normal learning and memory faster 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’#146;s the first time chemists have labeled and purified a solventfor imaging,’ she said.

    This may open up a whole new field of study into the effects of a wide arrayof solvents found in common everyday products from cleaning fluids to hairsprays.

    ‘There isn’#146;t a person among us who isn’#146;t exposed to solvents,’Dewey said.

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