Cocaine abuse and sensitization of striatal dopamine transmission: A critical review of the preclinical and clinical imaging literature

Much effort has been devoted in the preclinical addiction literature to understanding the phenomenon of sensitization, an enhanced dopaminergic response in the nucleus accumbens that occurs after repeated exposure to psychostimulant drugs. Although sensitization has been reported in preclinical studies, studies of sensitization in humans measuring behavioral and physiological responses have been mixed and inconclusive. However, imaging studies with positron emission tomography (PET) and single photon emission computed tomography (SPELT) using a stimulant challenge to induce dopamine (DA) release provide a unique opportunity to probe DA transmission in cocaine dependent human subjects. In contrast to the basic science literature that predicted sensitization, three independent cohorts have shown a blunted DA response, or the opposite of sensitization, in human cocaine dependent subjects. This article reviews the methodological differences between the preclinical and clinical PET studies that have investigated DA sensitization in order to address the discrepancy between the human and animal literature.