Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance in humans.
BACKGROUND
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.


OBJECTIVE
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.
Brain Sciences Institute, Swinburne University of Technology, Melbourne, Australia. kellis@bsi.swin.edu.au
Kathryn A
KA
Ellis
Mitul A
MA
Mehta
Keith A
KA
Wesnes
Stuart
S
Armstrong
Pradeep J
PJ
Nathan
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000009:adverse effects; D004294:Domperidone / Q000008:administration & dosage; D004298:Dopamine / Q000172:deficiency*; D004311:Double-Blind Method; D005425:Flicker Fusion / Q000187:drug effects; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009949:Orientation / Q000187:drug effects*; D010364:Pattern Recognition, Visual / Q000187:drug effects; D010479:Pergolide / Q000494:pharmacology*; D010649:Phenylalanine / Q000172:deficiency*; D017397:Prefrontal Cortex / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014443:Tyrosine / Q000172:deficiency*
D000596:Amino Acids; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010479:Pergolide; D014443:Tyrosine; D010649:Phenylalanine; D004294:Domperidone; D004298:Dopamine