Cocaine dependence: a disease of the brain's reward centers
Dackis CA, O'Brien CP.
Treatment Research Center,
University of Pennsylvania, 3900 Chestnut Street,
Philadelphia, PA 19104, USA.
[email protected]
Proc Natl Acad Sci U S A 2001 Apr 24; 98(9):5300-5305


Cocaine addiction affects brain reward centers that have evolved to ensure survival. Cocaine euphoria is intensely pleasurable and results from mesolimbic dopamine (DA) neurotransmission. DA signal-receiving neurons in the nucleus accumbens synthesize endogenous opioids and project to numerous reward regions. Cocaine-induced neuroadaptations, including DA depletion, may underlie craving and hedonic dysregulation. Cue-induced craving is vigorously triggered by conditioned elements of the drug environment and associated with measurable limbic activation. Reduced frontal lobe metabolism in cocaine-addicted individuals could explain important clinical phenomena such as denial and the loss of control over limbic impulses. Cocaine addiction is rapidly progressive and associated with severe medical, psychiatric, and psychosocial consequences. Denial shields addicted individuals from their predicament and must be addressed in treatment. Lacking pharmacological options, clinicians must rely entirely on psychosocial approaches. Treatment principles, including engagement, motivational enhancement, abstinence strategies, and craving reduction are discussed in terms of biological rationales.

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