The effects of acute tyrosine and phenylalanine depletion on spatial working memory and planning in healthy volunteers are predicted by changes in striatal dopamine levels

Rationale: Dopamine (DA) is considered important in the modulation of tasks of spatial working memory. However, the findings from studies in humans to date are mixed. While this may be due to the characteristics of the tasks used, it is also possible that these findings are explained by variable central effects of the manipulations used. Objective: To test the effects of acute tyrosine and phenylalanine depletion (TPD, which reduces synthesis and release of brain DA) on cognitive function and relate changes in performance accuracy to the central effects of TPD measured with [11C]raclopride positron emission tomography (PET). Methods: Fourteen participants were given tests of spatial working memory, planning, verbal memory span and trial-and-error learning after acute TPD, seven of whom also received PET scans to measure changes in striatal DA levels. Results: Although TPD produced a clear reduction in tyrosine and phenylalanine availability to the brain, no impairments on any of the cognitive tests were observed. However, changes in spatial working memory and planning accuracy after TPD showed a highly significant relationship with the changes in striatal DA levels. Conclusions: Our findings suggest that the effects of TPD on spatial working memory and planning may be unreliable due to the variability of the changes in brain DA levels achieved with this manipulation.