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Effect of acute tryptophan depletion on noradrenaline and dopamine in the rat brain

Division of Psychiatry and Neuroscience, Queen's University, Belfast, Northern Ireland, UK, t.ardis{at}qub.ac.uk

M. Cahir

Division of Psychiatry and Neuroscience, Queen's University, Belfast, Northern Ireland, UK

JJ Elliott

School of Psychology, Queen's University, Belfast, Northern Ireland, UK

R. Bell

School of Psychology, Queen's University, Belfast, Northern Ireland, UK

GP Reynolds

Division of Psychiatry and Neuroscience, Queen'7s University, Belfast, Northern Ireland, UK

SJ Cooper

Division of Psychiatry and Neuroscience, Queen's University, Belfast, Northern Ireland, UK

In human subjects, the acute tryptophan (TRP) depletion (ATD) paradigm has been shown to have effects on mood and cognition. It is assumed that these effects are mediated through the serotonin system. In this study, we have examined the effects of ATD on the central concentrations of the monoamine transmitters, noradrenaline (NA) and dopamine (DA) as well as on serotonin (5-HT). Effects on NA and DA could also affect mood and cognition. Following oral administration of TRP-containing (TRP+) and TRP-free (TRP–) amino acid mixtures, neurotransmitter concentrations and free plasma TRP concentrations were determined by High Performance Liquid Chromatography (HPLC) with electrochemical detection. Free plasma TRP was significantly and substantially reduced (79%) in rats given a TRP— amino acid mixture when compared with those given a TRP+ mixture. ATD also significantly decreased 5-HT and 5-hydroxyindolacetic acid in the frontal cortex, remaining cortex and hippocampus, but did not significantly reduce these in the striatum. Furthermore, ATD did not significantly alter the concentration of NA and DA in any brain region examined. This study demonstrates that the administration of a TRP– amino acid mixture in rats can reduce free plasma TRP to levels comparable to those reported in human studies. These results indicate that behavioural and cognitive changes produced by ATD in preclinical or clinical studies are likely to be due to specific effects on the serotonergic system.

Key Words: acute tryptophan depletion • dopamine • noradrenaline • rats • serotonin

This version was published on January 1, 2009

Journal of Psychopharmacology, Vol. 23, No. 1, 51-55 (2009)
DOI: 10.1177/0269881108089597


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