The death of Philip Seymour Hoffman this month has raised many questions about drug addiction, among them: What do drugs such as heroin do to the brain to make them so addictive? Can these chemical changes be undone?

Over the past 20 years, research into drug addiction has identified several chemical and physical changes to the brain brought on by addictive substances.

There is a wad of nerve cells in the central part of your brain, measuring about half an inch across, called the nucleus accumbens. When you eat a doughnut, have sex or do something else that your brain associates with survival and breeding, this region is inundated with dopamine, a neurotransmitter. This chemical transaction is partly responsible for the experience of pleasure you get from these activities.

Drugs such as heroin also trigger this response, but the dopamine surge from drugs is faster and long-lasting. When a person repeatedly subjects his nucleus accumbens to this narcotic-induced flood, the nerve cells that dopamine acts upon become exhausted from stimulation. The brain reacts by dampening its dopamine response — not just to heroin or cocaine, but probably to all forms of pleasurable behavior. In addition, some of the receptors themselves appear to die off. As a result, hyper-stimulating drugs become the only way to trigger a palpable dopamine response. Drug addicts seek larger and larger hits to achieve an ever-diminishing pleasure experience, and they have trouble feeling satisfaction from the things that healthy people enjoy.

Behavioral conditioning also plays a role. Once your brain becomes accustomed to the idea that eating a doughnut or having sex will provide pleasure, just seeing a doughnut or an attractive potential mate triggers the dopamine cascade into the nucleus accumbens. That’s part of the reason it is so difficult for recovering drug addicts to stay clean over the long term. Sights, sounds and smells associated with the drug high — needles, for example, or the friends with whom they used to get high — prime this dopamine response, and the motivation to seek the big reward of a drug hit builds.

Recent research suggests that the connection between these cues and the motivation to seek a high strengthens over time in the brain of a hardened addict, and this effect has been measured in the form of structural changes in the brains of laboratory animals.

Peter Kalivas, a neuroscientist at the Medical University of South Carolina, has a laboratory full of rats addicted to heroin, cocaine, nicotine, and other drugs. When he sounds a tone and flicks on a light, the rats know that their next hit will soon become available.

This cue sets off a series of events in the rats’ brains. An electrical signal travels along a neuron, then uses a chemical transmitter to make the jump to the next neuron. The more times the rat experiences the routine — tone and light, followed by a hit of drugs — the more efficiently the chemical signal is transmitted, thus solidifying the neural pathway between the cue and the desire to seek drugs. While the drug-seeking pathway strengthens in the brain of addicted animals, their ability to make alternative pathways diminishes. Researchers refer to this as a loss of plasticity.

“Cues that are not coding directly for the drug cannot produce good plasticity in the brain of an addict,” says Kalivas. “The system can’t learn.”

People who are addicted to drugs for years accumulate a large number of cues that lead them to seek out a high. Eventually, so much of their life becomes associated with getting high that it becomes nearly impossible for them to resist the urge. Going to work makes them think of getting high. Watching television makes them think of getting high. Finishing a meal makes them think of getting high.

The situation is not necessarily hopeless. Some pharmaceuticals are being studied that may help degrade transmission along the neural pathway that leads from the cue to the craving for drugs. But until there is a medical solution, it helps to replace the negative voice in an addict’s head with the supportive voices of friends and family, redirecting him from the desire to seek drugs. The plasticity of an addicted brain is diminished, not eliminated.