Eric Nestler, at the University of Texas, has shown how addiction causes permanent changes in the brains of animals. A single dose of many addictive drugs will produce a protein called DeltaFosB, that accumulates in the neurons. Each time the drug is used, more DeltaFosB accumlates, until it throw a genetic switch, affecting which genes are turned on or off. Flipping this switch causes changes that persist long after the drug is stopped, leading to irreversible damage to the brain's dopamine system and rendering the animal far more prone to addiction. Non drug addictions, such as running and sucrose drinking, also lead to the accumulation of DeltaFosB and the same permanent change in the dopamine system.

The addict experiences cravings because his brain has become sensitized to the drug or the experience. Sensitization is different from tolerance. As tolerance develops, the addict needs more and more of a substance to get a pleasant effect; as sensitization develops, he needs less and less of the substance to crave it intensely. So sensitization leads to increased wanting, though not necessarily liking. It is the accumulation of DeltaFosB, caused by exposure to an addictive substance or activity, that leads to sensitization.

The fact is that most alcholics, for reasons yet obscure, have lost the power of choice in drink.