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Another emerging theme is that of progressive brain changes and end-organ damage resulting from sustained abuse of drugs. Behavioural abnormalities associated with addiction are very long-lived. It is being increasingly appreciated that chronic drug exposure causes stable changes in the brain at the molecular and cellular levels that underlie these behavioural abnormalities [74].

A recent study with methamphetamine users illustrates this point. While illicit stimulants are often used to enhance attention and alertness and generally speed up the thought process, chronic users had a dose-dependent decrease of performance in neuropsychological tests that assess recall, ability to manipulate information, ability to ignore irrelevant information, and abstract thinking [75]. A positron tomography study in methampheta-mine abusers revealed an association of dopamine transporter reduction with psychomotor impairment [76]. A parallel study from the same group of investigators found higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers [77]. These results suggest that, in humans, methamphetamine abuse results in lasting changes in the function of dopamine- and non-dopamine-innervated brain regions.

One such molecular switch underlying long-term neural plasticity is DeltaFosB, a transcription factor that has been implicated in drug addiction and movement disorders [78].

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