>>936907001
The brain learns by adapting to every drug that affects its function. Some of these changes are relatively transient, like tachyphylaxis in an occasional drinker, but as learning is stronger with repetition, chronic exposure to a drug results in more lasting alterations. For some drugs, such as antidepressants, adaptation is actually the therapeutic point. Developing tolerance to selective serotonin reuptake inhibitors (SSRIs) may help to change a pathological affective “set point” so that being depressed is no longer the patient’s normal state.

With abused drugs, however, such changes are a real drag. As the brain adapts to a drug of abuse and the drug becomes less effective at stimulating dopamine transmission, a user must take more and more to produce the same high. Engaged in a futile attempt to replicate the initial experiences, an addict repeatedly administering the drug ensures more and more adaptation. Cocaine addiction demonstrates this desperate state starkly: addicts feel compelled to use, often despite full knowledge of the tremendous social, economic, and personal costs. Abstinence, to the user’s well-adapted mesolimbic circuitry, feels uninspired and hopeless, but a bump of cocaine doesn’t produce as much of a high in this lower-than-normal baseline state. Eventually, the best the addict can hope for is transient alleviation of chronic despair.