title: Acute tryptophan depletion in C57BL/6 mice does not induce central serotonin reduction or affective behavioural changes.
abstract: Acute tryptophan depletion is extensively used to investigate the implication of serotonin in the onset of depressive disorders. In rats, it lowers peripheral tryptophan and decreases central serotonin concentrations. We aimed to establish the rat model of acute tryptophan depletion in the mouse for potential application as serotonin challenge tool in genetic mouse models of depression. Pharmacokinetic and behavioural effects of a tryptophan-free diet were examined in Swiss and C57BL/6 mice. Peripheral amino acids were measured and central tryptophan and serotonin concentrations were compared with anxiety and depression-like behaviour in the elevated zero-maze, forced swimming test or tail suspension test. While acute tryptophan depletion resulted in a 74% reduction of the plasma ratio tryptophan to the sum of other large neutral amino acids in Swiss mice 1h after administration (2x10 ml/kg, 30 min interval), there was only a 40% reduction in C57BL/6 mice. The latter did not show anxiety in the elevated zero-maze or increased immobility in the forced swimming test or tail suspension test. A higher dose (2x20 ml/kg) with a longer interval (60 min) reduced the ratio with 68% in C57BL/6 mice, lowered hippocampal serotonin turnover and had no functional effect when tested in the elevated zero-maze and forced swimming test. These findings have important implications for the use of acute tryptophan depletion in general and in particular for its application in mice. Although in healthy mice no clear central serotonin or functional effects were observed, further research is indicated using mice with pre-existing serotonin dysfunction, as they might be more vulnerable to acute tryptophan depletion.
authors.affiliation: Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands. eva.vandonkelaar@np.unimaas.nl
authors.forename: Eva L
authors.initials: EL
authors.lastname: van Donkelaar
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.forename: Cindy K J
authors.initials: CK
authors.lastname: Lieben
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.forename: Linda
authors.initials: L
authors.lastname: Ferrington
authors.forename: Paul A T
authors.initials: PA
authors.lastname: Kelly
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D000208:Acute Disease; D000339:Affect / Q000502:physiology; D000818:Animals; D001008:Anxiety Disorders / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D005526:Food, Formulated; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019964:Mood Disorders / Q000378:metabolism* / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
chemical_list: D012701:Serotonin; D014364:Tryptophan