title: Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.
abstract: BACKGROUND
  The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness.
  
  
  METHODS
  The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity.
  
  
  RESULTS
  The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice.
  
  
  CONCLUSIONS
  1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.
authors: Proteesh
authors: P
authors: Rana
authors: Amit K
authors: AK
authors: Sharma
authors: Smita
authors: S
authors: Jain
authors: Pravin
authors: P
authors: Deshmukh
authors: S K
authors: SK
authors: Bhattacharya
authors: B D
authors: BD
authors: Banerjee
authors: Pramod K
authors: PK
authors: Mediratta
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000633:toxicity*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D016896:Treatment Outcome; D014364:Tryptophan / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D001500:BCG Vaccine; D005473:Fluoxetine; D014364:Tryptophan