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. 2007 Dec;195(3):377-85.
doi: 10.1007/s00213-007-0908-7. Epub 2007 Aug 23.

Lack of evidence for reduced prefrontal cortical serotonin and dopamine efflux after acute tryptophan depletion

Geoffrey van der Plasse  1 , Dorie T J Meerkerk, Cindy K J Lieben, Arjan Blokland, Matthijs G P Feenstra
Affiliations

Lack of evidence for reduced prefrontal cortical serotonin and dopamine efflux after acute tryptophan depletion

Geoffrey van der Plasse et al. Psychopharmacology (Berl). 2007 Dec.

Abstract

Rationale: Acute tryptophan depletion (ATD) is a widely used method to study the role of serotonin (5-HT) in affect and cognition. ATD results in a strong but transient decrease in plasma tryptophan and central 5-HT synthesis and availability. Although its use is widespread, the evidence that the numerous functional effects of ATD are caused by actual changes in 5-HT neuronal release is not very strong. Thus far, decreases in 5-HT efflux (thought to reflect synaptic release) were only reported after chronic tryptophan depletion or when ATD was combined with blockade of 5-HT reuptake.

Objective: With the current experiment, we aimed to study the validity of the method of ATD by measuring the extent to which it reduces the efflux of 5-HT (and dopamine) in the prefrontal cortex in the absence of reuptake blockage.

Materials and methods: We simultaneously measured in freely moving animals plasma tryptophan via a catheter in the jugular vein and 5-HT and DA efflux in the medial prefrontal cortex through microdialysis after ATD treatment.

Results: ATD reduced plasma tryptophan to less than 30% of control, without affecting 5-HT or DA efflux in the prefrontal cortex, indicating that even strong reductions of plasma tryptophan do not necessarily result in decreases in central 5-HT efflux.

Conclusion: The present experiment showed that reductions in plasma tryptophan, similar to values associated with behavioural effects, do not necessarily reduce 5-HT efflux and suggest that the cognitive and behavioural effects of ATD may not be (exclusively) due to alterations in 5-HT release.

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Figures

Fig. 1
Fig. 1
Plasma tryptophan concentration. Relative concentration (mean±SEM) of tryptophan in plasma compared to baseline. Open triangles correspond to the TRP minus group; closed squares correspond to the control group. The vertical grey bars correspond to, respectively, first diet administration, second diet administration and novelty exposure. Asterisk indicates a significant difference between the two groups, p < 0.05; sigma indicates a significant difference compared to the baseline value, p < 0.05
Fig. 2
Fig. 2
Microdialysis of 5-HT and DA and general activity counts. Relative change in extracellular 5-HT and DA (mean±SEM) and movement compared to baseline. Open triangles correspond to the TRP minus group; closed squares correspond to the control group. a 5-HT, b DA and c movement counts. The vertical grey bars correspond to, respectively, first diet administration, second diet administration and novelty exposure. No significant changes were observed
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