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A depressive phenotype induced by Bacille Calmette Guérin in ‘susceptible’ animals: sensitivity to antidepressants

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Abstract

Rationale

The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized.

Objectives

This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam.

Materials and 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.

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Acknowledgments

The authors wish to acknowledge Drs. James E. Barrett and Paul McGonigle for their continued support and valued suggestions throughout these studies and Dr. Jed Shumsky for his help with statistical analyses. In addition, the authors thank Ms. Nailah Barry and Ms. Ankita Narayan for their technical contributions. This research was funded by Drexel University College of Medicine. Salary for B. Platt was funded in part by a grant from the Merck Investigator Studies Program.

Conflict of interest

There are no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, MS488, Philadelphia, PA, 19102, USA

    Brian Platt, Nicole Klee, Maryam Nizami & Janet A. Clark

  2. University Laboratory Animal Resource Center, Drexel University College of Medicine, 245 North 15th Street, MS488, Philadelphia, PA, 19102, USA

    Janet Schulenberg

Authors
  1. Brian Platt
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  2. Janet Schulenberg
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  3. Nicole Klee
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  4. Maryam Nizami
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Correspondence to Janet A. Clark.

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Platt, B., Schulenberg, J., Klee, N. et al. A depressive phenotype induced by Bacille Calmette Guérin in ‘susceptible’ animals: sensitivity to antidepressants. Psychopharmacology 226, 501–513 (2013). https://doi.org/10.1007/s00213-012-2923-6

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  • DOI: https://doi.org/10.1007/s00213-012-2923-6

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