Ubiquitous Dopamine Deficit Hypotheses in Cocaine Use Disorder Lack Support
To the Editor: A recent article by Cassidy et al. (1), published in the November 2020 issue of the Journal, reported evidence that an MRI-based measure of midbrain dopamine concentrations, neuromelanin, is increased in individuals with a cocaine use disorder compared with healthy volunteers. The authors interpreted this to indicate that dopamine stores had been transferred from terminal region vesicles to the cytosol. This change, they proposed, might account for why people with substance use disorders exhibit reduced striatal dopamine responses to stimulant drug challenges. The finding is interesting, but I question whether it supports the view that mesostriatal dopamine function is reduced in stimulant users. As the authors acknowledge, the proposed model was speculative and post hoc; indeed, their previously reported validation studies found that increased midbrain neuromelanin concentrations index elevated dopamine release capacity (2). More importantly, accumulating studies indicate that striatal dopamine transmission is not “deficient” in people at risk for addictions (3, 4) or in those with current addictions (5–10). As a recent example, methylphenidate-induced striatal dopamine responses were larger in healthy volunteers than in people with a cocaine use disorder in one testing condition and larger in the cocaine-using group in a second condition (5). Given this literature, I propose that a more parsimonious interpretation of Cassidy and colleagues’ intriguing finding is that mesostriatal pathways in people with addictions differ from healthy subjects in multiple ways, yet the potential for increased dopamine transmission is retained, differing only in when it is expressed.
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