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A depressive phenotype induced by Bacille Calmette Guerin in 'susceptible' animals: sensitivity to antidepressants
Journal article   Peer reviewed

A depressive phenotype induced by Bacille Calmette Guerin in 'susceptible' animals: sensitivity to antidepressants

Brian Platt, Janet Schulenberg, Nicole Klee, Maryam Nizami and Janet A. Clark
PSYCHOPHARMACOLOGY, v 226(3), pp 501-513
01 Apr 2013
PMID: 23179968

Abstract

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry Science & Technology
The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized. This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam. CD-1 mice were dosed with Bacille Calmette-Gu,rin (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 na < ve 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). 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. 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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Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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