title: A depressive phenotype induced by Bacille Calmette Guérin in 'susceptible' animals: sensitivity to antidepressants.
abstract: BACKGROUND
  The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized.
  
  
  OBJECTIVE
  This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam.
  
  
  METHODS
  CD-1 mice were dosed with Bacille Calmette-Guérin (BCG) and measures of body weight, locomotor activity, and immobility in the tail suspension test (TST) were made. Spleen weight, plasma cytokines, and lung indoleamine-2,3-dioxygenase mRNA assessments were made at experiment termination. Pharmacological studies with acute fluoxetine and desipramine were done in naïve CD-1 mice to establish doses using the TST and in a locomotor assay to establish a nonsedating dose of diazepam. Characterization of the pharmacological sensitivity of the BCG model was done by assessing locomotor activity 6 days post BCG treatment and measuring immobility at 7 days post treatment in the presence or absence of fluoxetine (56 mg/kg), desipramine (20 mg/kg), or diazepam (1 mg/kg).
  
  
  RESULTS
  Ten to 30 % of BCG-treated mice did not exhibit an increase in immobility and were termed "resilient" to BCG-induced behavioral changes despite evidence of an activated immune system. BCG-"susceptible" mice exhibited increased immobility in TST and deficits in locomotor activity. The increased immobility in BCG-susceptible mice was attenuated by acute fluoxetine and desipramine, and exacerbated by diazepam.
  
  
  CONCLUSIONS
  The depressive phenotype in this BCG model of chronic inflammation is sensitive to antidepressants and consistent with clinical reports showing that paroxetine pretreatment prior to immunotherapy can prevent the development of psychiatric symptoms.
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, MS488, Philadelphia, PA 19102, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Platt
authors.forename: Janet
authors.initials: J
authors.lastname: Schulenberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Klee
authors.forename: Maryam
authors.initials: M
authors.lastname: Nizami
authors.forename: Janet A
authors.initials: JA
authors.lastname: Clark
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001500:BCG Vaccine / Q000008:administration & dosage; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010641:Phenotype
chemical_list: D000928:Antidepressive Agents; D001500:BCG Vaccine; D005473:Fluoxetine; D003975:Diazepam; D003891:Desipramine