Dopamine D2/D3 receptor availability and working memory in stimulant use disorder

<i>Background:</i> Dopaminergic neurochemical markers are associated with working memory performance in healthy participants and patients with schizophrenia. Individuals with stimulant use disorder have below-control levels of dopaminergic markers, such as striatal D2-type receptor (D2/3 R) availability (i.e. D2 + D3 subtypes), and they underperform healthy controls on tests of working memory. <i>Objectives:</i> For consideration in the design of treatments for stimulant use disorder, we tested whether working memory and D2/3 R availability are related in this population. <i>Methods:</i> Eighty-four adults with stimulant use disorder at varying lengths of abstinence (74 with methamphetamine use disorder, 10 with cocaine use disorder; 61/23 male/female) and 47 control subjects (26/21 male/female) completed the Spatial Capacity Delayed Response Task (SCAP), a test of working memory. In the stimulant group only, a subset (<i>n</i> = 52) underwent positron emission tomography (PET) using the D2/3 R ligand [¹⁸F] fallypride. Correlation between SCAP performance and D2/3 R availability was tested in bilateral cortical regions of interest previously associated with working memory (frontal, parietal, insular, and cingulate). <i>Results:</i> Controlling for demographics and estimated intelligence, participants in the stimulant group underperformed the control group on the SCAP (F(1, 125) = 5.58, <i>p</i> &lt; .05). In the subset of the stimulant group who received PET, SCAP performance was positively related to D2/3 R availability in the cingulate cortex (β = 0.43, <i>p</i> &lt; .013, Bonferroni corrected). <i>Conclusion:</i> The findings suggest that the weakness in working memory in participants who use stimulants reflects a deficit in cortical D2/3 R signaling. Strategies to augment cortical D2/3 R signaling may enhance cognitive function to improve treatment response.