jueves, 17 de noviembre de 2011

Sub-chronic dietary tryptophan depletion – An animal model of depression with improved face and good construct validity

M. Franklina, I. Bermudeza, H. Murckc, d, 1, N. Singewaldb, S. Gaburrob, 2
a School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK
b Department of Pharmacology and Toxicology, Institute of Pharmacy and Centre for Molecular Biosciences, Innsbruck, University of Innsbruck, Innsbruck, Austria
c Bristol-Myers Squibb, Pennington, NJ, USA
d Clinic of Psychiatry and Psychotherapy, Philipps-University of Marburg, Germany


Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression.

Aims were to test the hypothesis and optimise the time of SCTD-induced depression-related behaviour and associated biochemical changes.

Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days.

Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST).

Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine.

SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP.

Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased.

5-HT2 receptor binding Bmax was enhanced but was reversed by paroxetine.

Corticosterone and aldosterone were significantly negatively-correlated to weight gain.

SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine.

Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days.

Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour.

Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants.

Keywords: Tryptophan depletion; Serotonin; Behaviour; Corticosterone; Aldosterone; Kynurenine

fuente: Journal of Psychiatric Research

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