Study M147
Study name | Eskelund A 2017 |
Title | Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression-like behavior |
Overall design | Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague-Dawley rats. In Experiment 1 (acute treatment in SD rats), 72 SD rats were divided into the following 3 groups: (1) SD acute control group, (2) SD acute vortioxetine group, (3) SD acute ketamine group. Rats were treated i.p. with single dose of vehicle, vortioxetine (10 mg/kg), and ketamine (15 mg/kg), respectively. Rats were euthanized by decapitation 2, 4, 6, and 8 h later. The right hemisphere tissue and plasma were quickly removed. In Experiment 2 (acute treatment in FSL and FRL rats), FSL (n = 22) and FRL (n = 18) rats were divided into the following 8 groups: (4) FSL acute control group, (5) FSL acute fluoxetine group, (6) FSL acute vortioxetine group, (7) FSL acute ketamine group, (8) FRL acute control group, (9) FRL acute fluoxetine group, (10) FRL acute vortioxetine group, (11) FRL acute ketamine group. Rats were treated i.p. with single dose of vehicle, fluoxetine (10 mg/kg), vortioxetine (10 mg/kg), and ketamine (15 mg/kg), respectively. Rats were euthanized by decapitation 4 h later. Plasma and brain tissues, including hypothalamus, frontal cortex, hippocampus, striatum, midbrain, cerebellum, and rest of brain, were quickly removed. In Experiment 3 (sustained treatment to FSL, FRL, and SD rats), FSL (n = 32), FRL (n = 16) and SD (n = 32) rats were divided into the following 12 groups: (12) FSL sustained control group, (13) FSL sustained fluoxetine group, (14) FSL sustained vortioxetine group, (15) FSL sustained ketamine group, 16) FRL sustained control group, (17) FRL sustained fluoxetine group, (18) FRL sustained vortioxetine group, (19) FRL sustained ketamine group, (20) SD sustained control group, (21) SD sustained fluoxetine group, (22) SD sustained vortioxetine group, (23) SD sustained ketamine group. Rats were treated with 14 days of vehicle, fluoxetine (160 mg/L by drinking water, with the average daily dietary dose of 13.3 mg/kg), vortioxetine (600 mg/kg by food, with the average daily dietary dose of 48 mg/kg), and ketamine (15 mg/kg every 3rd day i.p.), respectively. Animals were killed the day after the last injection. Plasma, whole liver, and brain tissues, including hypothalamus, frontal cortex, hippocampus, striatum, midbrain, cerebellum, and rest of brain, were removed. |
Study Type | Type2; Type3; |
Data available | Unavailable |
Organism | Rat; Sprague-Dawley rat; |
Categories of depression | Healthy individuals; Healthy individuals; Healthy individuals; Animal model; Other animal model; Other animal model; |
Criteria for depression | Not reported |
Sample size | 192 |
Tissue | Central; Brain; Hippocampus; Central; Brain; Striatum; Central; Brain; Frontal cortex; Peripheral; Blood; Plasma; Peripheral; Liver; Liver; Central; Brain; Brain; Central; Brain; Hypothalamus; Central; Brain; Midbrain; Central; Brain; Cerebellum; |
Platform | MS-based; LC-MS: Waters Acquity HPLC system with Waters Quattro Premier XE triple quadrupole mass spectrometer (Waters Corporation, Milford, MA, USA); |
PMID | |
DOI | |
Citation | Eskelund A, Li Y, Budac DP, et al. Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression-like behavior. J Neurochem 2017; 142(1):118-31. |
Metabolite | L-Tryptophan; 5-Hydroxyindoleacetic acid; L-Kynurenine; |
