A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats

Rodrigo Moraga-Amaro, Cyprien G.J. Guerrin, Luiza Reali Nazario, Bruno Lima Giacobbo, Rudi A. J O Dierckx, Jimmy Stehberg, Erik F.J. de Vries, Janine Doorduin

Research output: Contribution to journalArticlepeer-review

Abstract

Worldwide, millions of people suffer from treatment-resistant depression. Ketamine, a glutamatergic receptor antagonist, can have a rapid antidepressant effect even in treatment-resistant patients. A proposed mechanism for the antidepressant effect of ketamine is the reduction of neuroinflammation. To further explore this hypothesis, we investigated whether a single dose of ketamine can modulate protracted neuroinflammation in a repeated social defeat (RSD) stress rat model, which resembles features of depression. To this end, male animals exposed to RSD were injected with ketamine (20 mg/kg) or vehicle. A combination of behavioral analyses and PET scans of the inflammatory marker TSPO in the brain were performed. Rats submitted to RSD showed anhedonia-like behavior in the sucrose preference test, decreased weight gain, and increased TSPO levels in the insular and entorhinal cortices, as observed by [11C]-PK11195 PET. Whole brain TSPO levels correlated with corticosterone levels in several brain regions of RSD exposed animals, but not in controls. Ketamine injection 1 day after RSD disrupted the correlation between TSPO levels and serum corticosterone levels, but had no effect on depressive-like symptoms, weight gain or the protracted RSD-induced increase in TSPO expression in male rats. These results suggest that ketamine does not exert its effect on the hypothalamic-pituitary-adrenal axis by modulation of neuroinflammation.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalStress (Amsterdam, Netherlands)
Volume25
Issue number1
DOIs
Publication statusPublished - 1 Jan 2022

Keywords

  • ketamine
  • major depressive disorder
  • Neuroinflammation
  • positron emission tomography
  • repeated social defeat

ASJC Scopus subject areas

  • Physiology
  • Neuropsychology and Physiological Psychology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Behavioral Neuroscience

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