Bacillus Calmette–Guérin vaccine induces a selective serotonin reuptake inhibitor (SSRI)-resistant depression like phenotype in mice

Vijaya Kumar, K. and Rudra, Anjuman and Sreedhara, M.V. and Siva Subramani, T. and Prasad, Durga Shiva and Das, Manish Lal and Murugesan, Senthil and Yadav, Rajbharan and Trivedi, Ravi Kumar and Louis, Justin V. and Li, Yu-Wen and Bristow, Linda J. and Naidu, Pattipati S. and Vikramadithyan, Reeba Kannimel (2014) Bacillus Calmette–Guérin vaccine induces a selective serotonin reuptake inhibitor (SSRI)-resistant depression like phenotype in mice. Brain, Behavior, and Immunity, 42. pp. 204-211. ISSN 08891591


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Preclinical studies have shown that administration of Bacillus Calmette–Guérin (BCG) vaccine induces depression-like behaviors in mice; however, the effect of antidepressant drug treatment has not been reported earlier. In the present study, we induced depression-like behavior by administering BCG vaccine to BALB/c mice. BCG treatment produced robust serum sickness as shown by a decrease in body weight, reduced spontaneous locomotor activity and reduced voluntary wheel running activity. BCG treatment also elevated plasma IL6 and IFNc levels and produced a marked activation of lung IDO activity. At a time point when serum sickness-related behaviors had fully recovered (i.e., day 14) BCG-treated mice showed a significant increase in immobility in the forced swim test (FST) and tail suspension test (TST) indicative of a pro-depressant phenotype. We observed significant increase in [3 H]PK11195 binding in cortex and hippocampus regions of BGC-treated mice in comparison to saline-treated mice indicating prominent neuroinflammation. Pharmacological evaluation of FST behavior in BCG-treated mice demonstrated selective resistance to the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and escitalopram. In contrast the tricyclic antidepressant imipramine, the dual serotonin/norepinephrine reuptake inhibitor (SNRI) duloxetine, and the dual dopamine/norepinephrine reuptake inhibitor (DNRI) nomifensine retained antidepressant efficacy in these mice. The lack of efficacy with acute treatment with SSRIs could not be explained either by differences in drug exposure or serotonin transporter (SERT) occupancy. Our results demonstrate that BCG-vaccine induced depression like behavior is selectively resistant to SSRIs and could potentially be employed to evaluate novel therapeutic agents being developed to treat SSRIresistance in humans.

Item Type: Article
Subjects: Pharmaceutical Sciences
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Dr Justin Louis
Date Deposited: 03 May 2017 08:10
Last Modified: 03 May 2017 08:10

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