Huffing, or inhalant abuse, is a significant problem among young people and the homeless due to the habit being cheap and easily accessible legally. It involves the concentration and inhalation of chemicals that are found in many household cleaners, solvents, glue, paint, etc, which result in the person feeling inebriated or “high.” At higher concentrations these chemicals can induce nausea, psychosis, memory loss, emotional disturbances, or violent behavior. One of the most common ingredients in abused inhalants is toluene (think the smell of paint thinner), an aromatic hydrocarbon which causes intoxication similar to alcohol inebriation when inhaled. Abuse over long periods of time can cause irreversible brain damage, as is often evidenced in chronic huffers, as well as changes in brain regions associated with reward and addiction.
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Until recently, it was unknown what the exact effect of toluene was and how its abuse resulted in addiction (and eventually, damage). It was suspected that solvents like toluene acted on all brain regions rather than a specific one (like most drugs), but in 2002, neurologist Stephen Dewey demonstrated that toluene acts specifically on the reward pathways of the brain: the ventral tegmental area (VTA) and the nucleus accumbens (ACB). Other drugs, like cocaine and nicotine, activate dopamine neurons in the VTA, which stimulates the release of dopamine into the VTA and ACB. They found that toluene had a similar effect on the VTA but was unable to demonstrate that it stimulated the ACB, which led to speculation that toluene exerted effect by a method other than dopamine.
However, a recent paper published in the January 2006 edition of Neuropsychopharmacology found that toluene also stimulated the ACB in a similar way to cocaine and nicotine. The authors (Riegel et al.) immersed rat brain slices in varying concentrations of toluene and found that lower concentrations were more potent: solutions of 1 micromolar and above didn’t activate the neurons, which explained why addicts prefer to administer in small amounts. They also injected small amounts of toluene into the brains of rats, and examined brain activation. They found that it stimulated the VTA (as previously found), but also dopamine was released into the ACB.