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