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

Background

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.

Objectives

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.

Methods

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 (n = 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).

Results

Controlling for demographics and estimated intelligence, participants in the stimulant group underperformed the control group on the SCAP (F(1, 125) = 5.58, p < .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, p < .013, Bonferroni corrected).

Conclusion

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.