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How high?
Sniffing toluene has the same neurological effects as cocaine and methamphetamine.

Jennie Woodcock/Reflections Photolibrary/CORBIS

A Huff Equals a Puff

Sniffing, or huffing, glue, paint, cleaning fluids, and nail polish remover may appear relatively harmless, but it is physiologically no different from other forms of drug abuse. That's the conclusion of a new study that shows that toluene, the solvent in many of these inhaled substances, has the same effect on our brains as notorious drugs like cocaine and methamphetamine. The findings explain a long-standing mystery about the impact of this addictive substance on the brain and suggest ways of developing treatments for addiction.

Solvent abuse increases a person's desire for other drugs, boosts the risk of depression and suicide, and irreversibly damages the brain, heart, kidney, and liver. But the exact effect of solvents such as toluene on our brains has remained unclear. Unlike other drugs that target specific areas of the brain, solvents were thought to act on all brain regions. Then, in 2002, neurologist Stephen Dewey of Brookhaven National Laboratory, in Upton, New York, and colleagues showed that toluene homes in on brain areas such as the reward center, which includes two main structures, the ventral tegmental area (VTA,) and the nucleus accumbens (ACB). Drugs such as nicotine and cocaine activate a group of dopamine-producing neurons in the VTA. These neurons start firing and release dopamine--the brain's feel-good chemical--into the VTA and the ACB. Later studies revealed that toluene also stimulates the neurons in the VTA to start firing. But no one was able to show whether it also induces them to release dopamine, leading some scientists to ask if toluene exerted its effects on the brain through a dopamine-independent pathway.

To get to the bottom of toluene's mechanism of action, neurologist Arthur Riegel of the Oregon Health and Science University in Portland and colleagues dunked rat brain slices in different concentrations of toluene and found that lower concentrations were more potent. Solutions of 1 ml Molar or more no longer activated the neurons, explaining why solvents are most potent when inhaled in small quantities. Next, the scientists injected small amounts of toluene into the brains of live rats. Not only did it electrically activate the VTA, it also caused the same neurons to release dopamine into the VTA and ACB, proving that toluene action on the brain is similar to that of other drugs. The team reports its findings online today in Neuropsychopharmacology.

The study is "a really outstanding piece of work," says Dewey. It answers the fundamental question about inhalant abuse, he notes: namely, what is the direct effect of the substance on dopamine in the brain's reward center? Researchers should now investigate whether they can curb toluene addiction using compounds that block dopamine receptors, he says.

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