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


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.


CONCLUSIONS
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.
van der Plasse
Geoffrey
G
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam ZO, The Netherlands. g.van.der.plasse@nin.knaw.nl
Meerkerk
Dorie T J
DT
Lieben
Cindy K J
CK
Blokland
Arjan
A
Feenstra
Matthijs G P
MG
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004032:Diet; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency*
D012701:Serotonin; D014364:Tryptophan; D004298:Dopamine
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