title: Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity.
abstract: 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-HT(2) 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.
authors.affiliation: School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK. mfranklin@brookes.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Franklin
authors.forename: I
authors.initials: I
authors.lastname: Bermudez
authors.forename: H
authors.initials: H
authors.lastname: Murck
authors.forename: N
authors.initials: N
authors.lastname: Singewald
authors.forename: S
authors.initials: S
authors.lastname: Gaburro
mesh_terms: D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000097:blood; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000097:blood; D003863:Depression / Q000209:etiology* / Q000473:pathology; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D007736:Kynurenic Acid / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood; D000080866:Nucleobindins; D017374:Paroxetine / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D014364:Tryptophan / Q000172:deficiency*
chemical_list: D000450:Aldosterone; D002135:Calcium-Binding Proteins; D002395:Catecholamines; D003345:Corticosterone; D004268:DNA-Binding Proteins; D007736:Kynurenic Acid; D007737:Kynurenine; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; D014364:Tryptophan