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Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance
Kathryn A Ellis1, Mitul A Mehta, Keith A Wesnes
1Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia. kellis@bsi.swin.edu.au
Rationale:
The mesocortical dopamine system is regarded as an important modulator of working memory. While it has been established that stimulation of the D1/D2 receptor in primates can improve spatial working memory performance, findings in humans are less consistent. Recent studies in humans suggest that global depletion of dopamine via tyrosine/phenylalanine depletion may impair spatial working memory performance, although these results are also inconsistent, and it has been suggested that task differences may partly underlie the inconsistent findings.
Objectives:
This study had two aims: (1) to investigate the effects of acute tyrosine depletion (TPD) on a number of working memory tasks and (2) to examine whether stimulation of D1/D2 receptors under conditions of TPD can attenuate or "reverse" TPD-induced working memory impairments.
Methods:
Eighteen healthy male participants performed a spatial working memory delayed-recognition task, non-spatial working memory task and spatial n-back task on three separate occasions, after TPD, TPD and pergolide (D1/D2 agonist), and placebo.
Results:
TPD did not impair working memory performance on any of the tasks administered. However, stimulation of D1/D2 receptors under TPD conditions caused a subtle impairment in spatial working memory performance.
Conclusions:
The finding that D1/D2 stimulation under TPD conditions impairs working memory highlights the complexity of functional effects of augmenting dopaminergic transmission within a dopamine-depleted state. The lack of TPD-related effects on a range of working memory tasks questions the reliability of TPD as a modulator of dopamine function and working memory performance in humans.
